Annual Meeting 2018 Highlights: Radiation Oncology

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2018 Annual Meeting Highlights Radiation Oncology is designed to help the busy radiation oncologist remain abreast of key scientific updates and cancer care strategies that relate to practice from the 2018 ASCO Annual Meeting. This expert-led education supplement provides a comprehensive collection on an array of key topics from the 2018 Annual Meeting relevant to the radiation oncologist. In addition, this supplement may also benefit medical oncologists, fellows, and advanced practice providers. 2018 Annual Meeting Highlights: Radiation Oncology is divided into six sections. Click the track links below to navigate quickly to the faculty summaries.

Breast - Gastrointestinal - Genitourinary - Gynecologic - Head & Neck - Melanoma - Thoracic - Additional Resources

 


 

Breast Cancer
Andrew Wahl, MD
Radiation Oncologist
University of Nebraska Medical Center

Fifteen-year results of the randomised EORTC trial 22922/10925 investigating internal mammary and medial supraclavicular (IM-MS) lymph node irradiation in stage I-III breast cancer. 
Oral Abstract Session
Philip Poortmans, MD
Abstract #504
Summary: Regional nodal RT in stage I-III breast cancer reduced breast-cancer mortality from 19.7% to 15.8% (p=0.005) and breast cancer recurrence from 27.1% to 24.5% (p=0.024). It should be noted that 44% were pN0. RT has a systemic effect. There was no difference in OS, DFS or distant disease-free survival. There was an increase in mortality from unknown causes in regional nodal RT arm, 3.1% vs 2.3%, p=0.01. The investigators are evaluating this discrepancy. 

TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score.
Plenary Session
Joseph A. Sparano, MD
Abstract #LBA1
Summary: Women with 1.1-5.0 cm invasive breast cancer, node negative, ER/PR positive, HER2 negative and 21 gene recurrence score (RS) of 11-25. In patients with RS 11-25, endocrine therapy (ET) was non-inferior to chemotherapy plus ET in IDFS, RFI, OS and distant recurrence. RS 0-10, distant failures are 2-3% with ET alone. RS 25-100, distant failures are 13% despite ET + chemotherapy. In women £ 50 years old who received ET + chemotherapy with RS of 16-20, there were 9% fewer IDFS events and 2% fewer distant relapses compared to ET alone; with RS of 21-25, there were 6% fewer IDFS events, most of which were due to fewer distant relapses.

Factors associated with lymphedema in patients/women with node positive breast cancer treated with neoadjuvant chemotherapy and axillary dissection on a prospective clinical trial.
Poster Discussion Session
Judy Boughey, MD
Abstract #513
Summary: ACOSOG Z1071 had a lymphedema (LE) substudy, where patients underwent prospective arm measurements after neoadjuvant chemotherapy (NACT) and at regular intervals after treatment. Severe LE (volume >20%) was 37.2% and was associated with longer duration of NACT. On multivariable analysis, obesity and length of NACT remained significant for LE symptoms.

 


 

Gastrointestinal Cancers
Daniel T. Chang, MD
Radiation Oncologist
Stanford, CA

Modified FOLFOX6 with or without radiation in neoadjuvant treatment of locally advanced rectal cancer: Final results of the Chinese FOWARC multicenter randomized trial.
Track: Colorectal
Oral Abstract Session
Yanhong Deng, MD, PhD
Abstract #3502
Summary: For patients with stage II and III rectal cancer, there was no difference in local recurrence (p=0.832), disease free survival (p=0.97), or overall survival (p=0.092) among preoperative 1) concurrent 5-FU and radiation, 2) concurrent FOLFOX and radiation, or 3) FOLFOX alone. There was no benefit to adding radiation to preoperative FOLFOX chemotherapy for DFS and OS. Preoperative FOLFOX alone did not have a worse LR rate compared to 5-FU and radiation.

Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine +/- oxaliplatin in locally advanced rectal cancer: Final results of PETACC-6.
Track: Colorectal
Oral Abstract Session
Hans-Joachim Schmoll, MD, PhD
Abstract #3500
Summary: For patients with stage II/III rectal cancer, there was no difference in local-regional relapse (p=0.238), distant relapse (p=0.261), DFS (p=0.84), or OS (p=0.252) between concurrent capecitabine with radiation vs CAPOX with radiation followed by TME and adjuvant CAPOX. There was no difference in DFS or OS by treatment arm for either stage II or stage III subgroup. There was a significant difference in DFS by treatment arm in patients treated outside Germany but not for German patients.

Long-term results of the ADORE trial: Adjuvant oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) versus 5-fluorouracil and leucovorin (FL) after preoperative chemoradiotherapy and surgery for locally advanced rectal cancer.
Track: Colorectal
Oral Abstract Session
Yong Sang Hong, MD, PhD
Abstract #3501
Summary: For patients with ypT3-4 or ypN+ rectal cancer, there was an improvement in DFS for adjuvant FOLFOX vs FL (6-year DFS 68.2% vs 56.8%, p=0.018). There was a significant benefit in DFS for stage ypIII patients with adjuvant FOLFOX vs FL (6-year DFS 63.2% vs 48.3%, p=0.019) but not for stage ypII patients (6-yr DFS 77.8% vs 69.5%, p=0.245). There was no difference in OS between the 2 arms for the overall group or by yp-stage.

A multi-center, randomized, prospective study evaluating the optimal radiation dose of definitive concurrent chemoradiation for inoperable esophageal squamous cell carcinoma.
Track: Non-colorectal
Poster Discussion Session
Yanjun Xu
Abstract #4013
There was no benefit in local-regional progression free survival, progression free survival, or overall survival with escalating the dose of radiation from 50 Gy to 60 Gy when combined with cisplatin and docetaxel for the definitive treatment of esophageal squamous cell carcinoma. There was no difference in local relapse or in-field local relapse with 60 Gy vs 50 Gy of radiation. There was no increase in severe toxicity with 60 Gy vs 50 Gy or radiation. 

Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer (PREOPANC-1) : A randomized, controlled, multicenter phase III trial.
Track: Non-colorectal
Oral Abstract Session
Geertjan Van Tienhoven, MD, PhD
Abstract #LBA4002
Summary: There was no difference in the resection rate between patients with resectable and borderline resection pancreatic cancer treated with preoperative chemoradiation vs. surgery and postoperative chemotherapy (60% vs 72%, p=0.065), but the R0 resection rate was superior with preoperative chemoradiation (63% vs 31%, p<0.001). Patients treated with preoperative chemoradiation had improved OS (median 17.1 months vs 13.7 months, p=0.074), DFS (median 9.9 months vs 7.9 months, p=0.023), disease metastases free interval (HR 0.71, p=0.013), and local-regional recurrence free survival (HR 0.55, p=0.002). The median OS for the R0/R1 resection group was 42.2 months with preoperative chemoradiation and 16.8 months with upfront surgery (p=0.001). Results show benefit of preoperative chemoradiation for resectable and borderline resectable pancreatic cancer.

Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas.
Track: Non-colorectal
Oral Abstract Session
Thierry Conroy, MD
Abstract #LBA4001
Summary: Adjuvant FOLFIRINOX improved median DFS from 12.8 months to 21.6 months (p<0.0001) compared to adjuvant gemcitabine following resection for pancreatic cancer. Adjuvant FOLFIRINOX improved median OS from 35 months to 54.4 months (p=0.003) compared to adjuvant gemcitabine following resection for pancreatic cancer. Adjuvant FOLFIRINOX was associated with worse hematologic and non-hematologic toxicity. Adjuvant FOLFIRINOX represents a new standard of care following resection for pancreatic cancer.

 


 

Genitourinary Cancers
Neha Vapiwala, MD
Radiation Oncologist
Hospital of the University of Pennsylvania 

A randomized phase III trial between adjuvant docetaxel and surveillance after radical radiotherapy for intermediate and high risk prostate cancer: Results of SPCG-13 trial.
Oral Abstract Session
Pirkko-Liisa Irmeli Kellokumpu-Lehtinen, MD, PhD
Abstract #5000
Summary: Adjuvant docetaxel without prednisone following definitive radiotherapy (RT) did not improve biochemical disease-free survival (BDFS) compared to post-RT surveillance in patients with intermediate- or high-risk prostate cancer (PC). Febrile neutropenia was a notable side effect in the docetaxel arm (16%). Although docetaxel has demonstrated benefit in higher-risk M0 and M1 hormone-naive disease, the intermediate-risk patients in this study did not benefit from this more intensive systemic therapy approach relative to standard of care RT. The population in which docetaxel may have greater likelihood of benefiting than early-stage prostate cancer is in those with low-volume oligometastatic prostate cancer.

A randomized study of finite abiraterone acetate (AA) plus leuprolide (LHRHa) versus LHRHa in biochemically recurrent non metastatic hormone naïve prostate cancer (M0HNPC).
Oral Abstract Session  
Eleni Efstathiou, MD, PhD  
Abstract #5002  
Summary: Treatment with abiraterone acetate together with leuprolide in nonmetastatic hormone-naïve prostate cancer improved the primary endpoint of PSA-free survival, as compared to leuprolide. Abiraterone acetate is appealing as it avoids delay in testosterone recovery and is well-tolerated. Most common AEs were Grade 1 hot flashes (71%) and fatigue (51%) with no difference between arms. Although this is a positive study, the long-term impact on patient survival from the added expense of abiraterone therapy is unknown.  

A randomized phase 2 study investigating 3 dosing regimens of radium-223 dichloride (Ra-223) in bone metastatic castration-resistant prostate cancer (mCRPC). 
Oral Abstract Session 
Cora N Sternberg, MD, FACP  
Abstract #5008  
Virtual Meeting 
Summary: Standard dosing (SD) for Ra-223 (55 kBq/kg every 4 weeks x 6 cycles) improved overall survival (OS) and delayed time to symptomatic skeletal events (SSEs) in patients with mCRPC and bone metastases. (Parker C, N Engl J Med. 2013;369(3):213-23). A similar patient population was randomized 1:1:1 to Ra-223 SD vs. high dose (88 kBq/kg every 4 weeks for up to 6 cycles) vs. Ra-223 SD every 4 weeks but extended for up to 12 cycles. No statistically significant differences in the primary objective was seen in SSE-free survival between SD vs. the high dose and extended dose arms [median 12.3 vs 12.9 months, hazard ratio (HR) 1.06 and median 13.2 vs 10.8 months, HR 1.26, respectively]. Median OS was 15.8, 16.0 and 14.4 months in the SD, HD and EXT arms, respectively. A total of 370 pts received Ra-223 with a median number of doses of 6 in each arm. Most frequent adverse events were fatigue, anemia and nausea. The high dose and extended dose arms had a higher incidence of grade ≥3 TEAEs than the standard dose arm. The currently approved dose and schedule of Ra-223 remains the standard of care. 

 


 

Gynecologic Cancer
William Small, Jr., MD, FACRO, FACR, FASTRO
Radiation Oncologist
Loyola University Medical Center

Outcomes and cost of open, robotic and laparoscopic radical hysterectomy for stage IB1 cervical cancer
Oral Abstract Session
Daniel Jacob Margul 
Abstract #5502
Summary: This a National Cancer Database evaluation looking at 5-year survival of woman with Stage IB cervical cancer treated with radical hysterectomy either open or with a minimally invasive technique. The study notes 5-year survival decreased for cervical cancer with a tumor size > 2 cm for woman who had minimally invasive surgery compared with open surgery. Especially in patients with borderline indications for post-operative radiation – type of surgery may be a factor in determining adjuvant therapy.

Neoadjuvant chemotherapy with cisplatin and gemcitabine followed by chemoradiation with cisplatin in locally advanced cervical cancer: A phase II, prospective, randomized, trial. 
Poster Discussion Session
Samantha Silva
Abstract #5523
Summary: This is a prospective randomized trial looking at locally advanced cervical cancer stage IIB-IVA randomized to neoadjuvant Gemcitabine and Cisplatin followed by chemoradiation with Cisplatin and Radiation or chemoradiation alone. Progression Free Survival (PFS) at 3 years was 41.1.% in the neoadjuvant chemotherapy group versus 59.6% in the chemoradiotherapy group with overall survival rates of 74.2% versus 81.9%. Adds to the literature that neoadjuvant chemotherapy should not be delivered in cervical patient treated with definitive chemoradiotherapy unless done on a clinical trial.

 


 

Head & Neck Cancers
Joseph K. Salama, MD
Radiation Oncologist
Duke University Medical Center

Definitive cetuximab-based (CRT-CX) vs. non-cetuximab based chemoradiation (CRT) in older patients with squamous cell carcinoma of the head and neck (HNSCC): Analysis of the SEER-Medicare linked database.  
Oral Abstract Session  
Dan Paul Zandberg, MD  
Abstract #6001  
Virtual Meeting
Summary: Radiotherapy and concurrent chemotherapy (CRT) and radiotherapy and cetuximab (cetuxRT) are standard treatment options for fit young patients. Comparison trials have not reported. The primarily elderly-population based data, found CRT had improved survival compared to those treated with cetuxRT or radiotherapy alone. Selection bias likely exists, although the data suggest that fit patients, should be considered for CRT and the use of cetuxRT should be cautiously used in this setting. 

Are women with head and neck cancer undertreated? 
Oral Abstract Session  
Annie Park  
Abstract #LBA6002  
Summary: ChemoRT is standard of care for locoregionally advanced head and neck cancer. In this population based analysis from Northern CA, women and men with HNC were more likely to die from cancer than other causes. Yet women were treated less frequently with intensive ChemoRT than men, despite controlling for other factors. This potential disparity needs to be validated and requires all clinicians to ensure that all patients regardless of sex get offered appropriate therapy. 

A phase II randomized trial of nivolumab with stereotactic body radiotherapy (SBRT) versus nivolumab alone in metastatic (M1) head and neck squamous cell carcinoma (HNSCC).  
Clinical Science Symposium Session  
Sean Matthew McBride, MD, MPH  
Abstract #6009    
Summary: Anti-PD1 monocolonal antibodies are active in recurrent and metastatic head and neck cancer. Anti- PD1 combination with SBRT has been shown safe in recent reports (PMID: 29437535), but no randomized comparisons exist comparing anti-PD 1 alone +/- SBRT in HNSCC. M1 HNSCC patients were randomized to anti-PD 1 +/- SBRT (mostly to lung metastases). No difference in OS, PFS, or response was seen with the addition of SBRT and should not be routine in this population for asymptomatic metastases.  

Results of a randomized, placebo (PBO) controlled, double-blind P2b trial of GC4419 (avisopasem manganese) to reduce duration, incidence and severity and delay onset of severe radiation-related oral mucositis (SOM) in patients (pts) with locally advanced squamous cell cancer of the oral cavity (OC) or oropharynx (OP).  
Oral Abstract Session  
Carryn M. Anderson, MD  
Abstract #6006    
Summary: 90 mg, but not 30 mg, of GC4419, infused daily for 60 min preRT, decreased grade 3-4 SOM duration, SOM development, grade 4 SOM development, and time to SOM development. FDA fast track/breakthrough designation given--a phase III study is planned. Orthostatic hypotension and 60 min IV preRT infusion pose logistical considerations to integration this agent into routine head and neck cancer care, although the potential benefits outweighs this consideration. 

 


 

Melanoma 
Joseph K. Salama, MD  
Radiation Oncologist  
Duke University Medical Center

Adjuvant therapy with nivolumab (NIVO) versus ipilimumab (IPI) after complete resection of stage III/IV melanoma: Updated results from a phase III trial (CheckMate 238).  
Oral Abstract Session  
Jeffrey S. Weber, MD, PhD 
Abstract #9502  
Summary: Prior EORTC 18071 trial demonstrated that adjuvant ipilimumab (10 mg/kg) improved RFS, DMFS, and OS compared to placebo, and therefore this trial compared treatment with nivolumab vs ipilimumab. This presentation updated prior presentations now with 24-month endpoints. Adjuvant nivolumab improved all endpoints in all resected stage III patient subgroups as well as resected stage IV (to NED) patients. Benefit was also seen in BRAF mutated and wild type patients. Adjuvant nivolumab is a standard of care treatment that radiation oncologists are going to be seeing more and more often.  

Final analysis of DECOG-SLT trial: Survival outcomes of complete lymph node dissection in melanoma.  
Oral Abstract Session  
Ulrike M. Leiter, MD  
Abstract #9501   
Summary: Sentinel LN Biopsy is standard of care for resectable melanoma, as it gives prognostic information. One study (MSLT-II) did not show a benefit for completion LN dissection following pathologically involved SLB. Final results of DECOG-SLT confirmed MSLT-II as there was no difference in OS, recurrence free survival, distant metastasis free survival and therefore routine completion LN dissection for microscopic metastases is NOT recommended. Both MSLT-II and DECOG-SLT required frequent US surveillance of dissection beds and therefore routine imaging should be standard in these patients.  

Durable tumor regression and overall survival (OS) in patients with advanced Merkel cell carcinoma (aMCC) receiving pembrolizumab as first-line therapy.  
Oral Abstract Session  
Paul Nghiem, MD, PhD  
Abstract #9506    
Summary: Prior small reports with short follow-up have demonstrated activity of pembroluzimab and other anti-PD1 agents against advanced Merkel Cell Carcinoma. This presentation updated prior NEJM publication of 26 patients. 86% of patients able to complete protocol therapy, and Grade 3+ Treatment Related AE 28%, 1 death. ORR remains 56% (unchanged), response predicted within the first 3 month scan, and were durable. Median OS not reached, and median PFS was 16.8 months numerically 4-5x larger than with cytotoxic chemotherapy. 

 


 

Thoracic Cancers 
Puneeth Iyengar, MD, PHD  
Radiation Oncologist  
University of Texas Southwestern Medical Center 

Phase II Trial of Concurrent Chemoradiation with Consolidation Pembrolizumab in Patients with Unresectable Stage III NSCLC. 
Oral Abstract Session 
Greg Andrew Durm, MD  
Abstract #8500    
Summary: Until 2017, the obvious standard of care for unresectable stage III non-small cell lung cancer (NSCLC) was chemoradiation followed by adjuvant chemotherapy depending on the concurrent chemotherapy administered. With the PACIFIC trial, adjuvant immunotherapy in the form of durvalumab improved progression free survival dramatically and has become standard of care. This abstract evaluated whether another immunotherapy, the PD-L1 regulator pembrolizumab could improve outcomes in a single arm phase II study evaluating the drug’s use after chemoradiation for stage III NSCLC. Use of pembrolizumab in consolidation increased time to metastatic disease and death and progression free survival compared to historical controls, with promising overall survival findings and limited toxicity.  

A Phase II Study of SBRT for Operable T1N0M0 NSCLC Japan Clinical Oncology Group (JCOG 0403): Long Term Follow-up Results.  
Poster Discussion Session  
Yasushi Nagata, MD, PhD  
Abstract #8512  
Summary: With increasing use of SBRT for early stage, inoperable NSCLC patients, its role in operable patients is now being reviewed. JCOG 0403 is a phase II single arm study assessing SBRT for operable T1N0M0 NSCLC patients treated to 48Gy over 4 fractions. The 5 and 10-year survival for this patient population was 54% and 23.8%, respectively. Though 5 and 10-year survival were comparable to historical surgical series, local failures were high (9/64) at last follow-up, though salvage surgery was probably still an option. With higher doses, SBRT for operable NSCLC patients may become an effective, non-invasive therapy

 


 

ADDITIONAL RESOURCES

ASCO University

2017 Annual Meeting Highlights: Radiation Oncology

Radiation Oncology Primer (2017 Update) - an introductory course covering key areas in radiation oncology including: clinical concepts such as radiotherapy, commonly used terms and mechanisms of radiation oncology, and the patient experience while under treatment

Imaging - an overview of various imaging modalities and how they are used in oncology including: Introduction to Diagnostic Imaging, Interventional Radiology, Assessing Tumor Response, and New and Emerging Imaging Modalities

Cancer.Net

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