To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with locally advanced esophageal cancer.
ASCO convened an Expert Panel to conduct a ...systematic review of the more recently published literature (1999-2019) on therapy options for patients with locally advanced esophageal cancer and provide recommended care options for this patient population.
Seventeen randomized controlled trials met the inclusion criteria. Where possible, data were extracted separately for squamous cell carcinoma and adenocarcinoma.
Multimodality therapy for patients with locally advanced esophageal carcinoma is recommended. For the subgroup of patients with adenocarcinoma, preoperative chemoradiotherapy or perioperative chemotherapy should be offered. For the subgroup of patients with squamous cell carcinoma, preoperative chemoradiotherapy or chemoradiotherapy without surgery should be offered. Additional subgroup considerations are provided to assist with implementation of these recommendations. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.
We performed a Phase I dose-escalation study to explore the feasibility and safety of treating primary and metastatic liver tumors with single-fraction stereotactic body radiotherapy (SBRT).
Between ...February 2004 and February 2008, 26 patients were treated for 40 identifiable lesions. Nineteen patients had hepatic metastases, 5 had intrahepatic cholangiocarcinomas, and 2 had recurrent hepatocellular carcinomas. The prescribed radiation dose was escalated from 18 to 30 Gy at 4-Gy increments with a planned maximum dose of 30 Gy. Cumulative incidence functions accounted for competing risks to estimate local failure (LF) incidence over time under the competing risk of death.
All patients tolerated the single-fraction SBRT well without developing a dose-limiting toxicity. Nine acute Grade 1 toxicities, one acute Grade 2 toxicity, and two late Grade 2 gastrointestinal toxicities were observed. After a median of 17 months follow-up (range, 2-55 months), the cumulative risk of LF at 12 months was 23%. Fifteen patients have died: 11 treated for liver metastases and 4 with primary liver tumors died. The median survival was 28.6 months, and the 2-year actuarial overall survival was 50.4%.
It is feasible and safe to deliver single-fraction, high-dose SBRT to primary or metastatic liver malignancies measuring ≤5 cm. Moreover, single-fraction SBRT for liver lesions demonstrated promising local tumor control with minimal acute and long-term toxicity. Single-fraction SBRT appears to be a viable nonsurgical option, but further studies are warranted to evaluate both control rates and impact on quality of life.
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Although neoadjuvant chemoradiotherapy achieves low local recurrence rates in clinical stages II to III rectal cancer, it delays administration of optimal chemotherapy. We evaluated preoperative ...infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy.
Thirty-two patients with clinical stages II to III rectal cancer participated in this single-center phase II trial. All were candidates for low anterior resection with total mesorectal excision (TME). Patients were to receive six cycles of FOLFOX, with bevacizumab included for cycles 1 to 4. Patients with stable/progressive disease were to have radiation before TME, whereas responders were to have immediate TME. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX × 6 was recommended, but adjuvant regimens were left to clinician discretion. The primary outcome was R0 resection rate.
Between April 2007 and December 2008, 32 (100%) of 32 study participants had R0 resections. Two did not complete preoperative chemotherapy secondary to cardiovascular toxicity. Both had preoperative chemoradiotherapy and then R0 resections. Of 30 patients completing preoperative chemotherapy, all had tumor regression and TME without preoperative chemoradiotherapy. The pathologic complete response rate to chemotherapy alone was 8 of 32 (25%; 95% CI, 11% to 43%). The 4-year local recurrence rate was 0% (95% CI, 0% to 11%); the 4-year disease-free survival was 84% (95% CI, 67% to 94%).
For selected patients with clinical stages II to III rectal cancer, neoadjuvant chemotherapy and selective radiation does not seem to compromise outcomes. Preoperative Radiation or Selective Preoperative Radiation and Evaluation Before Chemotherapy and TME (PROSPECT), a randomized phase III trial to validate this experience, is now open in the US cooperative group network.
Over the past decade, there has been an increasing use of radiotherapy (RT) for the treatment of liver metastases. Most often, ablative doses are delivered to focal liver metastases with the goal of ...local control and ultimately improving survival. In contrast, low-dose whole-liver RT may be used for the palliation of symptomatic diffuse metastases. This review examines the available clinical data for both approaches. The review found that RT is effective both for local ablation of focal liver metastases and for palliation of patients with symptomatic liver metastases. However, there is a lack of a high level of evidence from randomized clinical trials.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
Clinical outcomes for patients with pancreatic adenocarcinoma (PAC) remain dismal. Local recurrences, proportions of margin positive surgical resections, and overall survival outcomes remain inferior ...in PAC than any other solid tumor. This stems from a current standard of care management approach that needs to be inspired and transformed with modern treatment techniques and novel therapeutic options. Radiation therapy has historically been a central component in the treatment of pancreatic adenocarcinoma; however, the role of radiation therapy has been called into question based on the publication of clinical trials with conflicting results. We present an overview of the rationale for radiation therapy in resectable, borderline resectable, and unresectable pancreatic adenocarcinoma. We further present a summary of emerging clinical data and future directions to improve outcomes in this devastating malignancy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Background
High-grade neuroendocrine carcinomas (HGNECs) of the colon and rectum are rare, constituting less than 1 % of colorectal cancers. The purpose of this study was to identify the natural ...history and oncologic outcomes of this disease, describe the use of surgery, and determine the clinical and pathological factors associated with outcomes.
Methods
Following Institutional Review Board approval, patients with HGNEC were identified from our institutional database. Patient charts and pathology reports were analyzed retrospectively for clinical and pathological factors.
Results
A total of 126 patients with a median follow-up of 9 months were identified. Median survival was 13.2 months, and 85 (67 %) patients had metastatic disease at diagnosis. Three-year overall survival (OS) was 5 and 18 % for patients with and without metastatic disease, respectively. Factors associated with improved OS on multivariable analysis were absence of metastatic disease and presence of an adenocarcinoma component within the tumor. In patients with metastatic disease, response to chemotherapy was the only factor associated with survival. In patients with localized disease, an adenocarcinoma component within the tumor was the only factor associated with survival. Resection of tumor was not associated with survival in either localized or metastatic disease.
Conclusion
High-grade colorectal NECs are extremely aggressive tumors with poor prognosis. Patients appear to have a marginally better prognosis if they present without metastatic disease, have an adenocarcinoma component within their tumor, or respond to chemotherapy. Surgery, particularly in the presence of metastatic disease, may not offer a survival benefit for the majority of patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
To compare heart and coronary artery radiation exposure using intensity-modulated radiotherapy (IMRT) vs. four-field three-dimensional conformal radiotherapy (3D-CRT) treatment plans for patients ...with distal esophageal cancer undergoing chemoradiation.
Nineteen patients with distal esophageal cancers treated with IMRT from March 2007 to May 2008 were identified. All patients were treated to 50.4 Gy with five-field IMRT plans. Theoretical 3D-CRT plans with four-field beam arrangements were generated. Dose-volume histograms of the planning target volume, heart, right coronary artery, left coronary artery, and other critical normal tissues were compared between the IMRT and 3D-CRT plans, and selected parameters were statistically evaluated using the Wilcoxon rank-sum test.
Intensity-modulated radiotherapy treatment planning showed significant reduction (p < 0.05) in heart dose over 3D-CRT as assessed by average mean dose (22.9 vs. 28.2 Gy) and V30 (24.8% vs. 61.0%). There was also significant sparing of the right coronary artery (average mean dose, 23.8 Gy vs. 35.5 Gy), whereas the left coronary artery showed no significant improvement (mean dose, 11.2 Gy vs. 9.2 Gy), p = 0.11. There was no significant difference in percentage of total lung volume receiving at least 10, 15, or 20 Gy or in the mean lung dose between the planning methods. There were also no significant differences observed for the kidneys, liver, stomach, or spinal cord. Intensity-modulated radiotherapy achieved a significant improvement in target conformity as measured by the conformality index (ratio of total volume receiving 95% of prescription dose to planning target volume receiving 95% of prescription dose), with the mean conformality index reduced from 1.56 to 1.30 using IMRT.
Treatment of patients with distal esophageal cancer using IMRT significantly decreases the exposure of the heart and right coronary artery when compared with 3D-CRT. Long-term studies are necessary to determine how this will impact on development of coronary artery disease and other cardiac complications.
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GEOZS, IJS, NUK, OILJ, UL, UM, UPUK
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management ...challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology , to patients seen in their own clinical practice. A 47-year-old woman was referred for management of a newly diagnosed rectal cancer. She presented with a 2-month history of rectal bleeding and change in bowel habits. She underwent a colonoscopy that demonstrated a 5-cm fungating, friable, and partially obstructing mass in the distal rectum, approximately 5 cm from the anal verge. The tumor was palpable on digital rectal examination on the anterior wall of rectum. The biopsy demonstrated a moderately differentiated invasive adenocarcinoma, microsatellite stable. A staging work-up, including a computed tomography scan of the chest, abdomen, and pelvis, demonstrated rectal wall thickening in the midrectum and small lymph nodes in the left perirectal fat. There was a nonspecific 3-mm right lower lobe pulmonary nodule. Rectal magnetic resonance imaging demonstrated a 3-cm mass arising from mid-distal rectum with minimal extension beyond muscularis propria into the mesorectal fat, but without invasion of mesorectal fascia ( Fig 1 ). There were at least three small mesorectal lymph nodes present; the largest rounded node measured up to 5 mm, and no additional pelvic lymphadenopathy was identified. Her carcinoembryonic antigen was 1.1, and all other laboratory studies were within normal limits. She was seen in the Colorectal Multidisciplinary Conference for a discussion of her treatment options.
This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body ...radiotherapy (SBRT).
Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT.
All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year.
Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.
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