Dwight E. Heron, MD, MBA, FACRO, FACR

  • Professor and Vice Chairman of Clinical Affairs, Department of Radiation Oncology
  • Professor of Otolaryngology

I provide oversight and supervision of clinical radiation oncology at UPMC CancerCenter/University of Pittsburgh Cancer Institute, which includes 22 cancer centers domestically and 5 cancer centers internationally. I am actively involved in resident and medical student teaching. My research interests include stereotactic radiotherapy for benign and malignant brain and body tumors, evaluation of PET/CT in staging and management of head and neck, lung, and a variety of other cancers including the use of 4D PET-CT for thoracic and abdominal malignancies as well as identifying and addressing factors contributing to differences in cancer care in various populations in western Pennsylvania.

Teaching Activities:

  • Residency Clinical Setting and Lectures: In 2015-2016 our 8 residents participated in over 1,500 hours of lectures, clinic precepting, and supervision through our residency program office.
  • Medical Students and Fellows: In 2015-2016 I mentored over 19 medical students, fellows, and undergrad students within the radiation oncology department at UPMC Shadyside.
  • SRS/SABR Training Program (Course Director)February 2012 to
    1. UPMC CancerCenter/D3/Varian                                                           present
    2. National physician and physicist training
  • Respiratory Motion Management Training Program (Course Director)April 2014 to
    1. UPMC CancerCenter/D3/Varian                                                           present

Invited Lectures:

  • “Is Hypo-Fractionation Going to be the Standard in the Next Decade?”Presented at the 3rd Annual UPMC International Symposium, Rome, Italy, September 15, 2015.
  • “Radiation Dose-Volume Effects in SBRT for Locally-Recurrent Previously-Irradiated Head and Neck Cancer.”Presented at the ASTRO 2015 Conference, San Antonio, TX, October 20, 2015
  • “Stereotactic Radiosurgery (SRS) for Spine Tumours: State-of-the-Art.”Presented at The 2015 International Symposium on Minimally-Invasive Oncology, Gleneagles Hospital, Singapore, November 21, 2015.
  • “Intensity-Modulated Radiation Therapy (IMRT) for Head and Neck Cancers.”Presented at the 2015 International Symposium on Advance in HPB Surgery and Radiation Oncology, Sedona Hotel, Myanmar, November 22, 2015.
  • “AERO – Accuray Users’ Community:Current State and Future Direction.”Presented at the Accuray/AERO Users’ Meeting, San Francisco, CA, April 10, 2016.
  • “Stereotactic Body Radiation Therapy for Recurrent Head & Neck Cancers:New Options, New Challenges.”Presented at the ASRT Lunch and Learn Program, Pittsburgh, PA, April 20, 2016.
  • “Advanced Oncology Services in Emerging Markets: Challenges & Opportunities.”Presented at the UPMC International Strategy Meeting, Rome, Italy, April
  • “Role of Conventional and Ablative Radiotherapy in the Management of Recurrent, Second Primary, and/or Previously Irradiated H&N Cancer.”Presented at the ASCO Annual Meeting, Chicago, IL, June 6, 2016.
  • “SBRT in the Management of Recurrent, Second Primary & Previously-Irradiated Head & Neck Cancers:New Options, New Challenges.”Presented at the RSS SRS/SBRT Scientific Meeting, Orlando, FL, June 18, 2016.
  • “Best of ASTRO – Lung Cancer.”Presented at the 2016 Best of ASCO & ASTRO Conference, Cluj-Napoca, Romania, June 24, 2016.

Editorial Boards:

  • 2003 to presentScientific Reviewer for Laryngoscope
  • 2003 to presentScientific Reviewer for American Journal of Clinical Oncology
  • 2005 to presentScientific Reviewer for World Journal of Surgical Oncology
  • 2005 to presentScientific Reviewer for Cancer
  • 2003 to present Scientific Reviewer for Gynecologic Oncology
  • 2009 to present Editorial Board – Radiation Medicine Rounds
  • 2009 to present Editor – Technology in Cancer Research and Treatment
  • 2010 to presentEditorial Board – Radiation Oncology Rounds
  • 2010 to presentEditorial Board – Radiation Medicine Rounds: Head and Neck Cancer (Demos Series in Oncology)
  • 2013 to presentAssociate Editorial Board – Radiation Oncology section of Frontiers in Oncology
  • 2014 to presentEditorial Advisory Board – Journal of Clinical Pathways

Representative Publications

Vargo JA, Verma V, Kim H, Kalash R, Heron DE, Johnson R, Beriwal S. Extended (5-year) Outcomes of Accelerated Partial Breast Irradiation Using MammoSite Balloon Brachytherapy: Patterns of Failure, Patient Selection, and Dosimetric Correlates for Late Toxicity. Int J Radiat Oncol Biol Phys. 2014 Feb 1;88(2): 285-91. [Epub ahead of print 2013 Nov 21]. PMID:24268787.

Schenken LL, Rakfal SM, Heron DE, Proctor JW, Wilson SS, Ricci EM.  Inexpensive Solutions to Enhance Remote Cancer Care in Community Hospitals.  Community Oncology. 2013 Nov:10(11): 316-324.

Li T, Li X, Yang Y, Zhang Y, Heron DE, Huq MS. Simultaneous reduction of radiation dose and scatter for CBCT by using collimators. Med Phys. 2013 Dec;40(12):121913. PMID:24320524

Vivas EX, Wegner R, Conley G, Torok J, Heron DE, Kabolizadeh P, Burton S, Ozhasoglu C, Quinn A, Hirsch BE. Treatment Outcomes in Patients Treated With CyberKnife Radiosurgery for Vestibular Schwannoma. Otol Neurotol. 2014.  Jan;35(1):162-70. PMID:24335934

Riley C, Yang Y, Li T, Zhang Y, Heron DE, Huq MS. Dosimetric Evaluation of the Interplay Effect in Respiratory-Gated RapidArc Radiation Therapy.  Med Phys. 2014 Jan; 41(1): 011715.  PMID:  24387507.

Horne ZD, Clump DA, Vargo JA, Shah S, Beriwal S, Burton SA, Quinn AE, Schuchert MJ, Landreneau RJ, Christie NA, Luketich JD, Heron, DE.  Pretreatment SUVmax Predicts Progression-Free Survival in Early-Stage Non-Small Cell Lung Cancer Treated with Stereotactic Body Radiation Therapy.  Radiat Oncol. 2014 Jan; 30;9:41. PMID:  24479954.

Horne ZD, Clump DA, Shah S, Vargo JA, Burton SA, Christie NA, Schuchert MJ, Landreneau RJ, Luketich JD, Heron DEPretreatment SUVmax as a Marker for Progression-Free Survival in Stage I NSCLC Treated With SBRT.  Pract Radiat Oncol. 2013 Apr-Jun;3(2 Suppl 1):S3-4. Epub 2013 Mar 25. PMID: 24674539

Allison RR, Ambrad AA, Arshoun Y, Carmel RJ, Ciuba DF, Feldman E, Finkelstein SE, Gandhavadi R, Heron DE, Lane SC, Longo JM, Meakin C, Papadopoulos D, Pruitt DE, Steinbrenner LM, Taylor MA, Wisbeck WM, Yuh GE, Nowotnik DP, Sonis ST.  Multi-institutional, randomized, double-blind, placebo-controlled trial to assess the efficacy of a mucoadhesive hydrogel (MuGard) in mitigating oral mucositis symptoms in patients being treated with chemoradiation therapy for cancers of the head and neck. Cancer. 2014 May 1;120(9):1433-40. PMID:24877167

Fernando HC, Landreneau RJ, Mandrekar SJ, Nichols FC, Hillman SL, Heron DE, Meyers BF, DiPetrillo TA, Jones DR, Starnes SL, Tan AD, Daly BD, Putnam JB Jr.  Impact of Brachytherapy on Local Recurrence Rates After Sublobar Resection: Results From ACOSOG Z4032 (Alliance), a Phase III Randomized Trial for High-Risk Operable Non-Small-Cell Lung Cancer.  J Clin Oncol. 2014 Jun 30. pii: JCO.2013.53.4115. [Epub ahead of print]. PMID:24982457

Michalski D, Huq MS, Bednarz G, Heron DE.  The Use of Strain Tensor to Estimate Thoracic Tumors Deformation.  Medical Physics. 2014 July 41(7):073503. PMID:  24989417

Ling DC, Kabolizadeh P, Heron DE, Ohr JP, Wang H, Johnson J, Kubicek GJ.  Incidence of Hospitalization in Patients with Head and Neck Cancer Treated with Intensity-Modulated Radiation Therapy.  Head Neck. 2014 Jul 2 [Epub ahead of print]. PMID:  24986324

Vargo JA, Ferris RL, Clump DA, Heron DE. Stereotactic body radiotherapy as primary treatment for elderly patients with medically inoperable head and neck cancer. Front Oncol. 2014 Aug 11; 4:214. PMID:25157336.

Davis KS, Vargo JA, Ferris RL, Burton SA, Ohr JP, Clump DA, Heron DE. Stereotactic body radiotherapy for recurrent oropharyngeal cancer - Influence of HPV status and smoking history. Oral Oncol. 2014 Nov; 50(11):1104-8. PMID:25175942

Wong RS, Vikram B, Govern FS, Petereit DG, Maguire PD, Clarkson MR, Heron DE, Coleman CN. National Cancer Institute's Cancer Disparities Research Partnership Program: Experience and Lessons Learned.  Front Oncol. 2014 Nov 3;4:303. PMID: 25405101

Quan K, Rajagopalan MS, Heron DE. Stereotactic Body Radiation Therapy Is a Cost-Effective Alternative to Intensity-Modulated Radiation Therapy. J Clin Oncol. 2014 Oct 20; 32(30): 3451. PMID:25185091

Rwigema JC, Nguyen D, Heron DE, Chen AM, Lee P, Wang PC, Vargo JA, Low DA, Huq MS, Tenn S, Steinberg ML, Kupelian P, Sheng K.  4π Noncoplanar Stereotactic Body Radiation Therapy for Head-and-Neck Cancer: Potential to Improve Tumor Control and Late Toxicity.  Int J Radiat Oncol Biol Phys. 2015 Feb 1;91(2):401-9. PMID: 25482301

Fernando HC, Landreneau RJ, Mandrekar SJ, Nichols FC, DiPetrillo TA, Meyers BF, Heron DE, Hillman SL, Jones DR, Starnes SL, Tan AD, Daly BD, Putnam JB, Alliance for Clinical Trials in Oncology.  Analysis of longitudinal quality-of-life data in high-risk operable patients with lung cancer: Results from the ACOSOG Z4032 (Alliance) multicenter randomized trial. J Thorac Cardiovasc Surg. 2014 Nov 13. [Epub ahead of print] PMID: 25500100

Ling DC, Vargo JA, Wegner RE, Flickinger JC, Burton SA, Engh J, Amankulor N, Quinn AE, Ozhasoglu C, Heron DE.  Postoperative stereotactic radiosurgery to the resection cavity for large brain metastases: clinical outcomes, predictors of intracranial failure, and implications for optimal patient selection.  Neurosurgery. 2015 Feb;76(2):150-7. PMID: 25549189

Rhieu BH, Rajagopalan MS, Sukumvanich P, Kelley JL, Ahrendt GM, Heron DE, Beriwal S.  Patterns of care for omission of radiation therapy for elderly women with early-stage breast cancer receiving hormonal therapy. Pract Radiat Oncol. 2015 Jan 22. [Epub ahead of print] PMID: 25620165

Zhao B, Yang Y, Li X, Li T, Heron DE, Saiful Huq M.  Is high-dose rate RapidArc-based radiosurgery dosimetrically advantageous for the treatment of intracranial tumors? Med Dosim. 2015 Spring;40(1):3-8.  PMID: 25645205.

Vargo JA, Ferris RL, Ohr J, Clump DA, Davis KS, Duvvuri U, Kim S, Johnson JT, Bauman JE, Gibson MK, Branstetter BF, Heron DE.  A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck.  Int J Radiat Oncol Biol Phys. 2015 Mar 1;91(3):480-8. Epub 2015 Jan 30. PMID:  25680594.

Rajagopalan MS, Flickinger JC, Heron DE, Beriwal S.  Changing practice patterns for breast cancer radiation therapy with clinical pathways: An analysis of hypofractionation in a large, integrated cancer center network.  Pract Radiat Oncol. 2015 Mar-Apr;5(2):63-9.  PMID: 25748004.

Xu KM, Quan K, Clump DA, Ferris RL, Heron DE.  Stereotactic ablative radiosurgery for locally advanced or recurrent skull base malignancies with prior external beam radiation therapy. Front Oncol. 2015 Mar 17;5:65. PMID: 25853093.

Holt DE, Gill BS, Clump DA, Leeman JE, Burton SA, Amankulor NM, Engh JA, Heron DETumor bed radiosurgery following resection and prior stereotactic radiosurgery for locally persistent brain metastasis.  Front Oncol. 2015 Apr 8;5:84. PMID: 25905042.

Gill BS, Clump DA, Burton SA, Christie NA, Schuchert MJ, Heron DESalvage stereotactic body radiotherapy for locally recurrent non-small cell lung cancer after sublobar resection and i(125) vicryl mesh brachytherapy.  Front Oncol. 2015 May 11;5:109.  PMID: 26029665.

Li T, Burton S, Flickinger J, Heron DE, Huq MS. SU-E-T-40: A Method for Improving Dose Gradient for Robotic Radiosurgery. Med Phys. 2015 Jun;42(6):3339. PMID: 26127706.

Lalonde R, Heron D, Readshaw A, Huq M.  SU-E-T-129: Are Knowledge-Based Planning Dose Estimates Valid for Distensible Organs? Med Phys. 2015 June;42(6):3361. PMID: 26127795.

Chapman BV, Rajagopalan MS, Heron DE, Flickinger JC, Beriwal S. Clinical Pathways: A Catalyst for the Adoption of Hypofractionation for Early-Stage Breast Cancer. Int J Radiat Oncol Biol Phys. 2015 Nov 15;93(4):854-61. Epub 2015 Aug 7.  PMID: 26530754

Quan K, Xu KM, Lalonde R, Horne ZD, Bernard ME, McCoy C, Clump DA, Burton SA, Heron DE. Treatment Plan Technique and Quality for Single-Isocenter Stereotactic Ablative Radiotherapy of Multiple Lung Lesions with Volumetric-Modulated Arc Therapy or Intensity-Modulated Radiosurgery.  Front Oncol. 2015 Oct 6;5:213. PMID: 26500888

Schenker Y, Arnold RM, Bauman JE, Heron DE, Johnson JT. An enhanced role for palliative care in the multidisciplinary approach to high-risk head and neck cancer. Cancer. 2016 Feb 1;122(3):340-3. Epub 2015 Oct 27. PMID: 26505177.

Pennathur A, Luketich JD, Heron DE, Schuchert MJ, Bianco V, Clump D, Burton S, Abbas G, Gooding WE, Ozhasoglu C, Landreneau RJ, Christie NA.  Stereotactic Radiosurgery/Stereotactic Body Radiotherapy for Recurrent Lung Neoplasm: An Analysis of Outcomes in 100 Patients.  Ann Thorac Surg. 2015 Dec;100(6):2019-24. PMID: 26387725.

Davis KS, Lim CM, Clump DA, Heron DE, Ohr JP, Kim S, Duvvuri U, Johnson JT, Ferris RL. Tumor volume as a predictor of survival in human papillomavirus-positive oropharyngeal cancer. Head Neck. 2016 Apr;38 Suppl 1.E1613-7. Epub 2015 Dec 17. PMID: 26681273.

Gebhardt BJ, Rajagopalan MS, Gill BS, Heron DE, Rakfal SM, Flickinger JC, Beriwal S.  Impact of dynamic changes to a bone metastases pathway in a large, integrated, National Cancer Institute–designated comprehensive cancer center network. Pract Radiat Oncol. 2015 Nov-Dec;5(6):398-405. Epub 2015 Jul 4. PMID: 26432676.

Quan K, Xu KM, Zhang Yongqian, Clump DA, Flickinger JC, Lalonde R, Burton SA, Heron DE. Toxicities Following Stereotactic Ablative Radiotherapy Treatment of Locally-Recurrent and Previously-Irradiated Head and Neck Squamous Cell Carcinoma. Seminars in Radiation Oncology. 2016 Apr; 26(2):112-9. Epub 2015 Nov 27. PMID: 27000507.

Li T, Ozhasoglu C, Burton S, Flickinger J, Heron DE, Huq MS.  A method to improve dose gradient for robotic radiosurgery. J Appl Clin Med Phys. 2015 Nov 8;16(6):5748. PMID: 26699588.

Kent MS, Mandrekar SJ, Landreneau R, Nichols F, DiPetrillo TA, Meyers B, Heron DE, Jones DR, Tan AD, Starnes S, Putnam JB Jr, Fernando HC.  Impact of Sublobar Resection on Pulmonary Function: Long-Term Results from American College of Surgeons Oncology Group Z4032 (Alliance).  Ann Thorac Surg. 2016 Jul;102(1):230-8. Epub 2016 Apr 19. PMID: 27101728.

Kent MS, Mandrekar SJ, Landreneau R, Nichols F, Foster NR, DiPetrillo TA, Meyers B, Heron DE, Jones DR, Tan AD, Starnes S, Putnam JB Jr, Fernando HC. A Nomogram to Predict Recurrence and Survival of High-Risk Patients Undergoing Sublobar Resection for Lung Cancer: An Analysis of a Multicenter Prospective Study (ACOSOG Z4032).  Ann Thorac Surg. 2016 Jul;102(1):239-46. Epub 2016 Apr 19. PMID: 27101729.

Horne ZD, Glaser SM, Vargo JA, Ferris RL, Balasubramani GK, Clump DA, Heron DE, Beriwal S.  Confirmation of proposed human papillomavirus risk-adapted staging according to AJCC/UICC TNM criteria for positive oropharyngeal carcinomas.  Cancer. 2016 Jul 1;122(13):2021-30. Epub 2016 Apr 25. PMID: 27111669.

Argiris A, Bauman JE, Ohr J, Gooding WE, Heron DE, Duvvuri U, Kubicek GJ, Posluszny DM, Vassilakopoulou M, Kim S, Grandis JR, Johnson JT, Gibson MK, Clump DA, Flaherty JT, Chiosea SI, Branstetter B, Ferris RL.  Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer.  Ann Oncol. 2016 Aug;27(8):1594-600. Epub 2016 May 13. PMID: 27177865.

Wong SJ, Heron DE, Stenson K, Ling DC, Vargo JA.  Locoregional Recurrent or Second Primary Head and Neck Cancer: Management Strategies and Challenges. Am Soc Clin Oncol Educ Book. 2016;35:e284-92. PMID: 27249734.

Ling DC, Vargo JA, Ferris RL, Ohr J, Clump DA, Yau WY, Duvvuri U, Kim S, Johnson JT, Bauman JE, Branstetter BF, Heron DERisk of Severe Toxicity According to Site of Recurrence in Patients Treated With Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer.  Int J Radiat Oncol Biol Phys. 2016 Jul 1;95(3):973-80. PMID: 27302512.

Ling DC, Vargo JA, Heron DE. Stereotactic Body Radiation Therapy for Recurrent Head and Neck Cancer.  Cancer J. 2016 Jul-Aug;22(4):302-6. PMID: 2744175.

He S, Gill BS, Heron DE, Kelley JL, Sukumvanich P, Olawaiye AB, Edwards RP, Comerci J, Beriwal S.  Long-term outcomes using adjuvant pelvic intensity modulated radiation therapy (IMRT) for endometrial carcinoma. Pract Radiat Oncol. 2016 Jun 15. pii: S1879-8500(16)30094-7. doi: 10.1016/j.prro.2016.06.005. Epub ahead of print. PMID: 27527897.

Albergotti WG, Davis KS, Abberbock S, Bauman JE, Ohr J, Clump DA, Heron DE, Duvvuri U, Kim S, Johnson JT, Ferris RL.  Association of pretreatment body mass index and survival in human papillomavirus positive oropharyngeal squamous cell carcinoma.  Oral Oncol. 2016 Sep;60:55-60. Epub 2016 Jul 7. PMID: 27531873.

Editorials:

Letter to the Editor - Rajagopalan MS, Beriwal S, Heron DE. Clinical Pathways:  A Tool to Transform Practice Patterns. In regard to Olson et Al and Ellsworth et al.  Int J Radiat Oncol Biol Phys. 2014 Dec 1;90(5):1258.  PMID: 25539376

Editorial Response - Vargo JA, Heron DE.  Clinical Application of Stereotactic Body Radiotherapy (SBRT): Cranium to Prostate. Front Oncol. 2015 Dec 7;5:266. eCollection 2015. PMID: 26697404

Research Grants

Faculty Support on Research grants is 18 percent.

Active Grants:

Grant:  R01 CA150980                                    06/01/12-03/31/17                   0.60 calendar

NIH/NCI                                              $465,832

Accountability for Cancer Care through Undoing Racism and Equity (ACCURE)

The Greensboro Health Disparities Collaborative and two Cancer Centers have joined together to specify structures built into cancer care systems that make cancer care vulnerable to institutional racism and investigate how they can be changed to reduce racial inequity in quality and completion of treatment for Stage 1-2 breast and lung cancer patients. Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) systems change intervention is informed by CBPR principles, the Undoing RacismTM framework, and findings from our preliminary studies.

PI: S. Cykert and E. Eng

Grant:  U10 CA180844-01                 03/01/14-02/28/19                    1.20 calendar

NCI/NCTN                                         $4,956,250

NCI NCTN- University of Pittsburgh Cancer Institute (UPCI) UPMC Cancer Center – National Clinical Trials Network Lead Academic Participating Site (LAPS)
As a Lead Academic Site of the NCI National Cancer Network, the UPCI intends to leverage its historical leadership in the cancer cooperative groups, as well as its sophisticated and vibrant clinical research programs, to reduce the burden of cancer through assistance in the conduct of large, multicenter, scientifically sound, important cancer clinical trials with the potential to change the standard of cancer care in the United States and worldwide.

PI: A. Brufsky, Co-PI:  D. Heron

Grant: (No grant #)                              10/02/13-12/31/16

Bristol-Myers Squibb Company                        $20,000

Utilization of Low Level Laser Therapy for Mitigation of Cetuximab and Radiation –Induced Dermatitis in Patients Receiving Definitive Therapy for Head and Neck Squamous Cell Carcinoma
PI:  M. Rajagopalan, Co-PI:  D. Heron and D. Clump

Ongoing Current Clinical Research for July 1, 2015 – June 30th, 2016:

Title: Phase II study for curative intent treatment for patients with oligometastatic disease at initial presentation (10-027)

Primary Outcome Measures: Feasibility of SRS/SBRT in patients with metastatic disease at initial presentation

Secondary Outcome Measures: 1.) Quality of life (as measured by FACT surveys). 2.) Local control of metastatic sites. 3.) Local control of primary site. 4.) Overall survival. 5.) Analysis of patterns of failure post-SRS

Intervention Details:

Radiation: Stereotactic Radiosurgery (SRS); Dose and fractionation will be dependent on the lesion location and lesion size, the exact fractionation and dose is at the discretion of the treating physician. A minimum of 48 hours must be used in between SRS treatments at each site. Note that patients can have SRS every day or multiple SRS sessions in one day as long as the minimum time for each treatment site is met. For example, if two lung lesions, adrenal, and liver sites were being treated, both lung sites could be treated Monday, Wednesday, and Friday, the liver on Tuesday, Thursday and the following Tuesday, and the adrenal on Monday, Wednesday, Friday of the second week.

Detailed Description:

Patients with oligometastatic disease (defined here as 5 or fewer sites of metastatic disease involving 3 or fewer organ systems) are potentially curable with stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) (collectively referred to as stereotactic body radiotherapy or SBRT) to the metastatic disease sites in combination with standard curative therapy to the primary site.

Title: Phase II study of stereotactic body radiation for patients with oligometastatic disease at recurrence (10-028)

Primary Outcome Measures: Phase II study to evaluate feasibility of stereotactic radiation (SRS) in patients with oligometastatic disease

Secondary Outcome Measures: 1.) Toxicity (as measured by common toxicity criteria version. 2.) Quality of life surveys (as measured by FACT quality of life studies). 3.) Local control of metastatic sites. 4.) Overall survival of patients as compared to historical norms. 5.) Analysis of patterns of failure post-SRS

Intervention Details:

Radiation: Stereotactic Radiosurgery (SRS); Dose and fractionation will be dependent on the lesion location and lesion size and is up to the exact fractionation and dose is at the discretion of the treating physician. A minimum of 48 hours must be used in between SRS treatments at each site. Note that patients can have SRS every day or multiple SRS sessions in one day as long as the minimum time for each treatment site is met. For example, if two lung lesions, brain, adrenal, and liver sites were being treated both lung sites could be treated Monday, Wednesday, and Friday and the adrenal, liver and brain lesions treated Tuesday, Thursday

Detailed Description:

Patients with limited disease recurrence, known as oligometastatic or oligorecurrent disease (defined here as 5 or fewer sites of metastatic disease) will benefit in terms of overall survival and disease progression from reduced tumor burden and improved local control via radiation to oligometastatic sites.

Title: Prospective evaluation of hypofractionated stereotactic radiosurgery for low and intermediate risk prostate cancer (Dr. Heron – PI 09-031)

Primary Outcome Measures: 1.) To determine, in both low-risk and intermediate-risk cohorts, the rates of acute and late grade 3 or higher GI and GU toxicity observed during a 24 month follow up. 2.) To estimate the rate of biochemical Disease-Free Survival

Secondary Outcome Measures: To determine the rate of local failure, the rate of distant failure, the overall survival, the quality of life in generic and organ-specific domains

Intervention Details: Radiation: Stereotactic Body Radiation Therapy (36.25 Gy in 5 fractions (7.25 Gy/fx) delivered over a 2-week period)

Detailed Description:  Radiosurgery should be ideal for treating prostate cancer because: targeting accuracy for static targets is excellent, with an error of about 1mm, it can adjust for intra-fractional organ motion, reducing the volume of the target PTV and therefore the dose to surrounding organs, by using over one-hundred non-conplanar beams, the dose gradient between the prostate and surrounding tissues may be superior to that achieved with conventional linear accelerators, the radiobiology of prostate cancer may favor large dose per fractions.

Title: Phase I/III study of image guided radiosurgery/SBRT for localized spine metastasis (09-082)

Outline:

This is a multicenter, phase II study followed by a randomized phase III study. Patients enrolled in the phase III portion are stratified according to the number of spine metastases to be treated (1 vs 2-3).

Phase II: Patients undergo 1 high-dose image-guided radiosurgery or stereotactic body radiotherapy (SBRT) treatment over 60 minutes.

Phase III: Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo 1 high-dose image-guided radiosurgery or SBRT treatment over 60 minutes.

Arm II: Patients undergo 1 standard-dose external beam radiotherapy treatment over 5 minutes.

Title: A Pilot Study of Stereotactic Body Radiation Therapy (SBRT) for Treatment of Liver Metastases (Dr. Heron – PI 09-051)

Primary Outcome Objective: To determine the maximum tolerated dose (MTD) and safety of SBRT for liver metastases using dose escalation.

Secondary Outcome Objectives: 1.)evaluate the local control associated with this local regional therapy. 2.) determine local response based on FDG-PET/CT compared to CT alone. 3.) evaluate the Health Related Quality of Life (HRQL) associated with this therapy.

Patient population: In order to be eligible for this study, patients must have liver metastases intended for treatment with a combined volume no more than 100 cm3 in size, ≤ 3 total lesions, or one lesion ≤ 6cm in greatest dimension. Patients will be required to have adequate pre-treatment baseline liver function, defined as total bilirubin ≤ 3mg/dl, albumin > 2.5mg/dl, and INR ≤ 2.3. Serum liver enzymes must be less than three times the upper limit of normal. Baseline renal function must be adequate with a creatinine < 1.8mg/dl or creatinine clearance > 50ml/min. Patients must be at least 18 years of age and able to give informed consent. They must have a Karnofsky Performance Status ≥ 70 and a life expectancy of at least 3 months. Eligible patients will have also had a FDG-PET/CT (or if insurance does not allow for a PET, then a contrast enhanced CT) scan performed at least 45 days prior to being enrolled in this study, with no chemotherapy within 4 weeks before SBRT and 2 weeks after.

Study design and methodology: This is a phase I dose escalation study. Dose escalation will be via the traditional “up and down” scheme

Treatments administered:

SBRT: Patients will receive one of the following radiation regimens: 1.) 50 Gy in 5 fractions (10 Gy/fx) delivered over a 2-week period. 2.) 60 Gy in 5 fractions (12 Gy/fx) delivered over a 2-week period. 3.) 75 Gy in 5 fractions (15 Gy/fx) delivered over a 2-week period.

Efficacy data collected: The following evaluations will be performed to assess the efficacy of stereotactic body radiation therapy: 1.) Locoregional control.  2.) Objective tumor response (by RECIST and EORTC 1999 criteria). 3.) Radiological assessment using FDG-PET/CT to evaluate local control compared to CT. 4.) Quality of life assessment, FACT-HEP score, a validated measure of HRQL in hepatobiliary disease.

Title: SBRT for close or positive margins after resection of pancreatic adenocarcinoma: A prospective evaluation in select patients with resected pancreas (Dr. Heron – PI 10-123)

Primary Outcome Objective: To determine the rate of local progression-free survival (LPFS) achieved in subjects with close (<2.5 mm) or positive margins after pancreatic cancer resection treated with SBRT

Seondary Outcome Objectives: c 1.) determine the time to progression (TTP) and overall survival (OS) evaluate the acute and late toxicities associated with SBRT in this patient population. 2.) evaluate quality of life (QOL) of locally-advanced pancreatic cancer subjects treated adjuvantly with SBRT

Subject population: Subjects with primary adenocarcinoma of the pancreas that has been resected with positive margins or close margins (<2.5 mm)

Study design and methodology: This is a phase II study

Treatments administered: 12 Gy x 3 fractions (36 Gy total)

Efficacy data collected: The following evaluations will be conducted to assess the efficacy of SBRT: 1.) Local progression-free survival (LPFS). 2.) Locoregional and distant control. 3.) Time-to-progression (TTP)

Title: A Phase III trial of Adjuvant Chemotherapy following Chemoradiation as Primary Treatment for Locally Advanced Cervical Cancer compared to Chemoradiation Alone: The OUTBACK Trial (Dr. Heron – PI RTOG 1174 – UPCI 12-038)

Patient Population:

All patients must have locally advanced cervical cancer suitable for primary treatment with chemoradiation with curative intent.     Patients  must  have  a  histologically  confirmed  diagnosis  of  squamous  cell  carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix with stage IB1 & positive nodes, IB2, II, IIIB or IVA disease.  All patients must have an ECOG performance status 0, 1, or 2.  Patients must NOT have received previous pelvic radiotherapy or chemotherapy for this tumor or require interstitial brachytherapy treatment at presentation.  Patients must NOT have para-aortic nodal involvement above the level of the common iliac nodes or L3/L4 (if biopsy proven, PET positive, or ≥ 15 mm short-axis diameter on CT) nor evidence of distant metastases. Patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervix cancer therapy are NOT eligible.  HIV positive patients are NOT eligible.

Primary Objective:  1.) To determine if the addition of adjuvant chemotherapy to standard cisplatin-based chemoradiation improves overall survival.
Secondary Objective:  1.) To determine the progression-free survival rates.  2.) To determine acute and long-term toxicities. 3.) To determine patterns of disease recurrence. 4.) To determine the association between radiation protocol compliance and outcomes. 5.) To determine patient quality of life, including psycho-sexual health.

Tertiary endpoints will be:  1.) To determine the association between the results of a follow-up PET scan performed 4 – 6 months post completion of chemoradiation and outcomes for all patients in the trial.  2.) To determine the biological predictors of patients' outcomes based on translational laboratory studies of blood and tissue specimens.

Title: Phase II Double-Blinded Placebo-Controlled Study of Bevacizumab With or Without AMG 386 in Patients With Recurrent Glioblastoma or Gliosarcoma (RTOG 1122 – UPCI 12-113)

Patient Population:

Histologically proven diagnosis of glioblastoma or variants (gliosarcoma, glioblastoma with oligodendroglial features, giant cell glioblastoma). Patients will be eligible if the original histology was a lower grade glioma and a subsequent histological diagnosis of glioblastoma or variants is made.  Patients must have shown unequivocal evidence for tumor progression on the previous treatment regimen (prior to enrollment on this study) by MRI scan of the brain with and without contrast within 14 days prior to registration. The dose of steroids must be stable or decreasing for at least 5 days prior to the scan. Patients unable to undergo MR imaging because of non-compatible devices can be enrolled, provided CT scans are obtained and are of sufficient quality. Patients without non-compatible devices may not have CT scans performed to meet this requirement.

Primary Objectives: 1.) To assess the safety and tolerability of AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1).  2.) To assess the efficacy of AMG 386 in combination with bevacizumab 10 mg/kg every 2 weeks compared to bevacizumab monotherapy in bevacizumab-naïve patients, as measured by 6-month progression-free survival (PFS6) (Cohort 2).

Secondary Objectives: 1.) To further assess the toxicity profile (Cohorts 1 and 2).  2.) To assess feasibility of AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks (Cohort 1), as measured by the percentage of patients requiring dose reduction/interruption or discontinuation in the first 2 and subsequent cycles.  3.) To  determine  the  radiographic  response  rate  (RR),  median  progression-free  survival  (PFS),  and  OS  in bevacizumab-naïve patients (Cohort 2).  4.) To assess the efficacy of AMG 386 15 mg/kg weekly in combination with bevacizumab 10 mg/kg every 2 weeks in patients who have progressed while on bevacizumab, as measured by overall survival (OS) (cross-over from placebo arm of Cohort 2).  5.)To  correlate  outcome  to  treatment  with  tumor  genotype,  expression  profile,  and  circulating  angiogenesis biomarkers in tumor specimens (Cohort 2).  6.) To determine the RR, PFS6, and PFS in patients who have progressed while on bevacizumab therapy and receive AMG 386 in combination with bevacizumab (cross-over from placebo arm of Cohort 2).  7.) To determine the plasma pharmacokinetics of AMG 386 in patients receiving bevacizumab (Cohort 1 and cross-over from placebo arm of Cohort 2).

Title: Randomized Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) with Cetuximab +/- Docetaxel followed by Adjuvant Cetuximab +/- Docetaxel in Recurrent, Previously-Irradiated Squamous Cell Carcinoma of the Head and Neck (SCCHN) (Dr. Heron – PI UPCI 11-112)

Objective:

Compare the overall survival of patients with the addition of docetaxel to the overall survival of patients treated with SBRT and cetuximab alone.  In addition, we will determine the difference in progression free survival (PFS), the rate of local recurrence (LR) and of distant metastases (DM) across the SBRT and cetuximab + docetaxel arm and the arm receiving SBRT and cetuximab alone.  To better resolve the impact of the experimental treatment on PFS, LR, and DM, patients will be stratified by the presence/absence of prior cetuximab treatment and then randomized  to either the control arm  (cetuximab and SBRT only) or the experimental arm (cetuximab, SBRT, and docetaxel).

Primary Objectives:

  1. To determine the 1-year locoregional progression-free survival (PFS) of previously-irradiated patients with SCCHN treated with SBRT, cetuximab, and docetaxel
  2. To evaluate the acute and late toxicities associated with the above therapy

Secondary Objectives:

  1. To evaluate the impact of adjuvant docetaxel and cetuximab on incidence of distant disease
  2. To determine the objective response rate, PFS, and overall survival (OS)
  3. To evaluate the impact of docetaxel on response rates with SBRT
  4. To assess the toxicity of combination docetaxel-cetuximab & SBRT
  5. To evaluate changes in tumor glucose metabolism post-therapy as assessed by FDG-PET
  6. To evaluate the expression of tumor-specific biomarkers before and after treatment
  7. To evaluate the impact of study interventions on patient-reported quality of life (PR-QOL)

Patient population: Patients with recurrent or second primary squamous cell carcinoma of the head and neck (SCCHN) with locoregionally-confined disease will be eligible to participate. Other criteria include ECOG PS <2 (KPS >60), normal hepatic and renal function, age >18, deemed to be medically or surgical inoperable or patient refusal of surgery.

Study design and methodology:  Open-label randomized 2-arm phase II

Treatment administered:

  1. Fractionated stereotactic radiosurgery: 8.8-10 Gy per fraction (total: 44-50 Gy)-dose is dependent on treatment volume
  2. Cetuximab: 400 mg/m2 day -7, then 250 mg/m2 days 0 & 8, then weekly for 3 months
  3. Docetaxel: 25 mg/m2 day 0 & 8, then weekly for 3 months

Title: Phase I Study of Fractionated Stereotactic Radiosurgery for Large Brain (Dr. Heron – PI UPCI 11-091)

Primary Objectives:  To determine the maximum tolerated dose (MTD) and safety of fractionated SRS when treating brain metastases

Secondary Objectives:

  1. To evaluate the local control associated with this therapy.
  2. To evaluate regional intracranial failure associated with this therapy.
  3. To evaluate the Health Related Quality of Life (HRQL) associated with this therapy.

Overall design and plan of study: Prior to enrollment, all patients will be evaluated with a physical exam, review of pathology and laboratory values to confirm diagnosis, and baseline imaging studies
Accelerator: Physicians will treat patients with linear accelerator-based stereotactic radiosurgery system using 6MV photons.

Doses:

Patients will receive a total dose of 24 to 36 Gy in 3 fractions (8-12 Gy/fx).  Dose will be escalated between patients as described in Section 7. In determining the radiation dose and fractionation scheme for this protocol, we used the linear-quadratic model for radiation cell killing to “equate” schemes that care the dose/fraction and number of fractions.  This concept of biologically equivalent dose (BED) states that the total effect is given by: n x d x (1 +d/(α/β)) where n is the number of fractions and d is the dose/fraction.  The “alpha-beta ratio” characterizes the radiation response of a particular tissue; a higher value is indicative of a tissue that responds acutely to the effects of radiation. Due to their highly proliferative nature, most tumors fall into this category. This first dose scheme (total dose 24 Gy) is biologically equivalent to the previously studied best recommended doses in the literature (15 Gy, one fraction). We would favor treating in three fractions, as opposed to a single dose, to allow more repair of normal tissue, reoxygenation of tumor cells, and redistribution of tumor cells to more radiosensitive parts of the cell cycle.  Using small fraction sizes, 8- 12 Gy, will also help reduce late effects of radiation therapy.  SRS treatment will be given on an every other day schedule, excluding weekends.  The prescription dose will be prescribed to the isodose line best encompassing the planning target volume (PTV) depending on the volume of tumor.

Title: Phase III Comparison of Thoracic Radiotherapy Regimens in Patients with Limited Small Cell Lung Cancer also Receiving Cisplatin and Etoposide (UPCI 11-121)

Primary Objective: To determine whether administering high dose thoracic radiotherapy, 70 Gy (2 Gy once-daily over 7 weeks) or 61.2 Gy (1.8 Gy once-daily for 16 days followed by 1.8 Gy twice-daily for 9 days), will improve median and 2-year survival compared with 45 Gy (1.5 Gy twice-daily over 3 weeks) in patients with limited stage small cell lung cancer.

The purpose of this study is to compare the effects, good and/or bad, of two different ways to give radiation therapy. One of the ways is experimental, while one of them is standard. The experimental way of giving the radiation therapy is once a day with a high dose of radiation for 7 weeks. The standard way of giving the radiation therapy is to give it twice a day for 3 weeks. Everyone will get the chemotherapy with cisplatin and etoposide, which has been established through clinical trials to be standard drugs (chemotherapy) for your type of cancer. The exact doses of the chemotherapy have not been completely standardized and you will be receiving a commonly used dosing schedule. It is not known what the added side effects are using this dose of chemotherapy with either of the radiotherapy regimens.

Title: A Phase Ib Trial of Concurrent Cetuximab (ERBITUX®) and Intensity Modulated Radiotherapy (IMRT) with Ipilimumab (YERVOY®) in Locally Advanced Head and Neck Cancer (UPCI 12-084)

Immune suppression in oropharynx cancer (OPC) is commonly observed and likely contributes to tumor progression. Cetuximab plus radiotherapy is clinical effective in OPC patients and evidence suggests that cetuximab induced immune stimulation, which might be enhanced through direct immunologic targeted therapy. The novel checkpoint inhibitor, ipilimumab, has not been evaluated in OPC before, and the desire to improve clinical results, as well as the high prevalence of human papillomavirus (HPV) infection as a major etiologic cause of OPC, warrant careful evaluation of immunotherapeutic approaches. Here we proposed to integrate anti-CTLA-4 specific mAb, ipilimumab, into a standard regimen of cetuximab plus RT (70-74.0 Gy) in a dose finding, phase I trial, to inform the design of a future phase II clinical trial which would determine clinical efficacy.

Specific Aims:  Establish a recommended starting dose of ipilimumab for a future efficacy trial when used in combination with intensity modulated radiation therapy (IMRT) and cetuximab

Subject Population:

All eligible patients will be “high risk” or “intermediate risk.” 

  • “High risk” is defined as 1) non-oropharyngeal subsite including larynx or hypopharynx (p16 status not required) or 2) HPV/p16- oropharynx subsite.
  • “Intermediate risk” is defined as HPV/p16+ oropharyngeal squamous cell cancer with: 1) ≥10pk-yr smoking history and ≥ N2 nodal disease, or 2) the presence of T4 tumor or N3 nodal disease, irrespective of smoking status.

In this eligible cohort, 2-year PFS ranges from 40% to 65%.

HPV status will be determined using p16 immunohistochemistry (IHC) in a CLIA-certified laboratory at UPMC/UPCI.

Treatment Plan:

Cetuximab/IMRT Plus Ipilimumab (14 Week Regimen)

IMRT, Weeks 2-8:   70-74.0 Gy with 2.0 Gy daily fractions delivered in 7-7.5 weeks

Cetuximab, Weeks 1-8

Week 1: 400 mg/m2

Weeks 2-8 (concurrent with IMRT):  250 mg/m2/week

Ipilimumab, Weeks 5, 8, 11, 14

Ipilimumab dose will be determined by cohort (1, 3, 6, or 10 mg/kg)

Title: Impact of Breast Conservation Surgery on Surgical Outcomes and Cosmesis in Patients with Multiple Ipsilateral Breast Cancers (MIBC) (UPCI 12-159)

Primary Clinical Goal: To assess the local recurrence (LR) rate with breast conservation in patients with multiple ipsilateral primary breast cancer (MIBC).

Purpose:  To determine whether breast conservation surgery, also called lumpectomy, the removal of only the tumor tissues from the breast, is as effective as mastectomy, or the removal of the entire breast, at keeping the cancer from returning.

This study is conducted by the American College of Surgeons Oncology Group (ACOSOG) through Alliance, a national collaboration of researchers and physicians with different types of background and training who work together to plan and conduct clinical trials in cancer that will lead to improved treatment strategies that will decrease suffering and death. Alliance members come from major academic medical centers, community hospitals and community practice.

Title: A Randomized Phase I/II Study of NAB Paclitaxel, or Paclitaxel, Plus Carboplatin with Concurrent Radiation Therapy Followed by Consolidation in Patients with Favorable Prognosis Inoperable Stage IIIA/B Non Small Cell Lung Cancer (NSCLC) (UPCI 13-001)

Primary Objective: To determine the 2-year overall survival from randomization for patients receiving

carboplatin/paclitaxel or carboplatin/nab-paclitaxel with radiation therapy

Patient Population: Histologically or cytologically documented NSCLC; Patients must be M0. Patients with T1-T2 with N2 or T3N1-2 are eligible, if inoperable. Patients with T4 with any N or any T with N2 or N3 disease are eligible if unresectable.

Required Sample Size: 6 total during the Phase 1 (Feasibility Testing)

92 during the Phase 2 (46 in Arm A, 46 in Arm B): total patient accrual is 98.

Title: Randomized Phase II Trial of Concurrent Bevacizumab and Re Irradiation Versus Bevacizumab Alone as Treatment for Recurrent Glioblastoma  (UPCI 13-009 RTOG 1205)

Primary Objective: To establish an improvement in overall survival in recurrent GBM patients receiving bevacizumab and re-irradiation compared with patients receiving bevacizumab alone.

Arm 1: Bevacizumab alone q 2 weeks (control arm)

Arm 2: Hypofractionated radiotherapy 35 Gy in 10 fractions with concurrent Bevacizumab q 2 weeks (experimental arm)

Patient Population: Patients with recurrent glioblastoma or variant (gliosarcoma or giant cell glioblastoma etc).

Title: A Phase III Study of Postoperative Radiation Therapy (IMRT) +/  Cetuximab for Locally Advanced Resected Head and Neck Cancer (UPCI 13-088 RTOG 0920)

Primary Objective: Test whether the addition of cetuximab to radiation therapy will improve overall survival (OS) inpostoperative patients with intermediate risk following surgery

Patient Population: Pathologically proven diagnosis of squamous cell carcinoma (including variants such as verrucouscarcinoma, spindle cell carcinoma, carcinoma NOS, etc.) of the head/neck (oral cavity, oropharynx or larynx); clinical stage T2-T4a, N0-2, M0 or T1, N1-2, M0.

Title: Phase II Randomized Trial of Transoral Surgical Resection followed by Low dose or Standard dose IMRT in Resectable p16+ Locally Advanced Oropharynx Cancer (UPCI 13-101)

Primary Objectives: Accrual, risk distribution, and surgical quality will be used to determine the feasibility of a prospective multi-institutional study of transoral surgery for HPV+ oropharynx cancer followed by risk-adjusted adjuvant therapy. To assess the oncologic efficacy following transoral resection and adjuvant therapy in patients determined to be at “intermediate risk” after surgical excision, the 2-year PFS rate will be examined.

Purpose:  To study the effects, good and/or bad of performing surgery through your mouth (what is referred to as transoral surgery) followed by treatment that is selected based on studying your cancer under a microscope by a doctor (called a pathologist), on you and your human papillomavirus associated oropharynx cancer. The study is being done because we think that the results of studying your cancer under the microscope can help us be more careful about how much extra treatment needs to be given after surgery.

Arm A: Low Risk – Observation

Arm B: Intermediate Risk – Radiotherapy IMRT 50 Gy/25 Fx

Arm C: Intermediate Risk – Radiotherapy IMRT 60 Gy/30 Fx

Arm D: High Risk - Radiotherapy IMRT 66 Gy/33 Fx + 3CDDP 40 mg/m2 weekly

Title: ERCC1 trial A randomized, phase II study of definitive radiotherapy with concurrent cisplatin vs. docetaxel-cetuximab in locally advanced head and neck squamous cell carcinoma: an ERCC1 biomarker enrichment and interaction design (UPCI 13-056)

Primary Objective: To evaluate the efficacy of radiotherapy with concurrent docetaxel-cetuximab vs. cisplatin in patients with PULA HNSCC and increased tumoral ERCC1 expression, as measured by time to progression (TTP)

The goal of this clinical research study is to learn which chemotherapy combination may be more effective in treating locally advanced head and neck squamous cell carcinoma. The side effects of these combinations will also be studied.

This study treatment consists of radiation therapy and study chemotherapy.  The study chemotherapy will be either cisplatin or a combination of Docetaxel and Cetuximab. The type of study treatment will e depend on the presence of ERCC-1 in the tumor.

ERCC-1 is a protein found in the body that helps to repair damaged DNA.  People have different amounts of this protein in their tumor.  Another reason this study is being done is to see which radiation and chemotherapy combination works best in relationship to how much ERCC-1 is expressed in a tumor.

Group A:  will receive cisplatin and radiation therapy on an outpatient basis.

Group B:  will receive cetuximab, docetaxel, and radiation therapy on an outpatient basis.

Title: Phase II Study Of Stereotactic Radiosurgery or Other Local Ablation Followed by Erlotinib for Patients with EGFR Mutation Who Have Previously Progressed on an EGFR Tyrosine Kinase Inhibitor (TKI) (UPCI 12-150)

The SOC radiosurgery incorporated in this multicenter protocol was referred to and specific for CyberKnife®. However, the intent of this protocol is not to dictate which SOC radiosurgery is used, as there are many brands of stereotactic radiosurgery. No core content has been modified. The new parameters will not affect in any way how stereotactic radiosurgery is done for UNC patients—it remains SOC. Similarly, it defines the SOC in such a way that parallel procedures will take part at our partner institutions so that their patients will also be treated per SOC.

Primary Objective: To estimate PFS after locally ablative therapy and erlotinib in EGFR-mutant NSCLC patients who progressed on prior EGFR-TKI therapy

Title: Randomized Phase II/III Trial of Surgery and Postoperative Radiation Delivered with Concurrent Cisplatin versus Docetaxel versus Docetaxel and Cetuximab for High-Risk Squamous Cell Cancer of the Head and Neck (13-057 RTOG 1216)

Randomized Phase II Component Primary Objective: To select the better experimental arm to improve disease-free survival (DFS) over the control arm of radiation and cisplatin

Phase III Component Primary Objective: To determine whether the selected experimental arm will improve overall survival (OS) over the control arm of radiation and cisplatin

Patient Population:

Patients with pathologic stage III or IV head and neck squamous cell carcinoma (HNSCC) involving the oral cavity, oropharynx (p16 negative), larynx, or hypopharynx. Patients must have at least 1 of the following high-risk pathologic features: extracapsular nodal extension or invasive cancer seen within 3 mm of the primary tumor resection margins.

Title: Phase I Study of AZD1775 (MK 1775) with Radiation and Temozolomide in Patients with Newly Diagnosed Glioblastoma and Evaluation of Intratumoral Drug Distribution in Patients with Recurrent Glioblastoma (13-125)

Patient Population: Newly diagnosed glioblastoma

Primary Objectives (Phase I):

  1. To determine the maximum tolerated doses (MTD) of AZD1775 (MK-1775) in combination with the current standard of care (radiotherapy/temozolomide for concomitant therapy and temozolomide for adjuvant therapy) for treating patients with newly diagnosed glioblastoma
  2. To define the MTD of AZD1775 (MK-1775) in combination with 6 weeks of daily (M-F) radiotherapy (RT) and concomitant temozolomide (TMZ) administered at 75 mg/m2/day in patients with newly diagnosed glioblastoma (Arm 1)
  3. To define the MTD of AZD1775 (MK-1775) in combination with adjuvant TMZ administered at 150 mg/m2/day-200 mg/m2/day for 5 days every 28 days in patients with glioblastoma after concurrent RT/TMZ (Arm 2)

Secondary Objectives:

  1. To characterize the safety profile of AZD1775 (MK-1775) in combination with RT and concomitant TMZ (Arm 1) and AZD1775 (MK-1775) with adjuvant TMZ (Arm 2) in patients with newly diagnosed glioblastoma
  2. To assess the pharmacokinetic (PK) profile of AZD1775 (MK-1775) in combination with upfront radiation/TMZ and adjuvant TMZ in patients with newly diagnosed glioblastoma

Phase I: Dose Finding: Cohorts of 3 patients (per Arm) until MTD is reached

Combination Dose Cohort: 12 patients

Intratumoral Drug Distribution: 12-18 patients

Title: Randomized Phase II Study of Neoadjuvant Chemotherapy (Gemcitabine and nab paclitaxel vs. mFOLFIRINOX) and Stereotactic Body Radiation for Borderline Resectable Pancreatic Cancer (13-143)

Study Population:  Subjects with primary borderline resectable adenocarcinoma of the pancreas (as defined by SSO criteria

Primary Objective:  Characterize the safety and efficacy of neo-adjuvant gemcitabine plus nab-paclitaxel in patients receiving SBRT and surgery for borderline resectable pancreatic cancer, using neo-adjuvant mFOLFIRINOX as a control.

Secondary Objective(s):

  1. To determine R0 resection rates in borderline resectable pancreatic cancer after treatment with gemcitabine/nab-paclitaxel or mFOLFIRINOX and SBRT
  2. To determine the safety and toxicity of preoperative chemotherapy and SBRT
  3. To determine radiological response rate to therapy
  4. To determine CA19-9 response to neoadjuvant chemotherapy and other serologic markers of response including HMGB1, sRAGE, DNA by picogreen, and IL-6
  5. To determine time to progression (TTP) in this population
  6. To determine predictive factors of response to chemotherapy with the use of correlative factors including SPARC, RM1, and SMAD4
  7. To assess absolute lymphocyte count at the beginning and end of therapy as potential novel markers of overall survival.
  8. To determine patients Quality of Life effects during chemotherapy and SBRT

Title: A Randomized Phase III Clinical Trial Evaluating Post Mastectomy Chestwall and Regional Nodal XRT and Post Lumpectomy Regional Nodal XRT in Patients with Positive Axillary Nodes Before  Neoadjuvant Chemotherapy Who Convert to Pathologically Negative Axillary Nodes After Neoadjuvant Chemotherapy (14-105 RTOG 1304)

Patient Population: Clinically T1–3, N1 Breast Cancer Documented Positive Axillary Nodes by FNA or by Core Needle Biopsy

Patient Randomization:
Arm 1:

  1. Radiation therapy for Group 1A
    1. Whole breast irradiation + boost
  2. No radiation therapy for Group 1B

Arm 2:

  1. Radiation therapy for Group 2A
    1. Whole breast irradiation + boost and regional nodal irradiation
  2. Radiation therapy for Group 2B
    1. Chest wall and regional nodal irradiation

Aim: To evaluate whether the addition of chestwall + regional nodal XRT after mastectomy or breast + regional nodal XRT after breast conserving surgery will significantly reduce the rate of events for invasive breast cancer recurrence-free interval (IBC-RFI) in patients who present with histologically positive axillary nodes but convert to histologically negative axillary nodes following neoadjuvant chemotherapy.

Endpoint: IBC-RFI, defined as time from randomization until invasive local, regional, or distant recurrence, or death from breast cancer.

Sample Size: The B-51/1304 study will enroll 1636 patients over a period of 5 years. It is anticipated that the definitive analysis will be carried out approximately 7.5 years after study initiation.

Title:  Phase II Study Determining The Efficacy Of Pre-Operative Stereotactic Radiosurgery Followed By Resection For Brain Metastases (14-150 – Dr. Heron – PI)

Patient Population:  Patients will have no more than 4 distinct lesions within the brain.  The target lesion must measure at least 15 mm in at least one dimension, and no more than 40mm in any dimension.

Primary Objective:

  1. To determine the local control rate in subjects with solitary brain metastases treated with pre-operative SRS followed by surgical resection.

Secondary Objective:

  1. To evaluate the overall survival.
  2. To evaluate distant intracranial failure associated with this therapy.
  3. To evaluate the Health Related Quality of Life (HRQL) associated with this therapy.
  4. To collect and store the resected body tissue(s) and blood samples for potential correlation to clinical outcome.

Title: A Prospective, Randomized Phase II Study of Surgery with or without Adjuvant Stereotactic Body Radiotherapy (SBRT) (14-151 Dr. Heron – PI)

Patient Population: Pathologically proven recurrent or second-primary head-and-neck cancer receiving prior radiotherapy with or without chemotherapy.

Primary Objective: To compare the 1-year local control in patients with operable, recurrent previously-irradiated squamous cell head-and-neck cancers with or without adjuvant SBRT.

Secondary Objectives:

  1. Determine the locoregional progression-free survival (PFS) distant PFS, overall PFS (local + regional + distant), and overall survival (OS).
  2. Evaluate the acute and late toxicities of adjuvant SBRT in the re-irradiation setting following salvage surgery.
  3. Determine prognostic factors that may predict the likelihood of local failure, regional failure, or OS in this cohort to guide future management.
  4. Compare the impact of adjuvant SBRT versus a wait-and-see approach on patient reported quality of life (PR-QoL).

Title:  A Randomized Phase II Trial For Patients With P16 Positive, Non-Smoking Associated, Locoregionally Advanced Oropharyngeal Cancer (UPCI 15-122 / NRG HN 002- Dr. Heron – Co PI)

Patient Population: Patients with pathologically proven diagnosis of squamous cell carcinoma (including the histological variants papillary squamous cell carcinoma and basaloid squamous cell carcinoma) of the oropharynx

Primary Objective:  To select the arm(s) achieving a 2-year progression-free survival rate of ≥ 85% without unacceptable swallowing toxicity at 1 year

Secondary Objectives: 

  1. To determine patterns of failure (locoregional relapse versus distant) and survival (overall and progression-free) at 6 months and 2 years;
  2. To determine acute toxicity profiles at the end of radiation therapy and at 1 and 6 months;
  3. To determine late toxicity profiles at 1 and 2 years;
  4. To determine patient-reported swallowing outcomes at 6 months and 1 and 2 years;
  5. To determine the predictive value of 12-14 week, post-treatment FDG-PET/CT for locoregional control and PFS at 2 years;
  6. To determine the predictive value of blood and tissue biomarkers for disease outcomes at 2 years.