Practical Considerations for the Treatment of an Adrenal Metastasis With Stereotactic Body Radiation Therapy.

The purpose of this paper is to summarize 3 methods for treating adrenal metastases with stereotactic body radiation therapy. This article is not meant to provide consensus guidelines but rather to present 4 practical examples of treatment techniques using different treatment platforms from 3 institutions.

Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review.

BACKGROUND: A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT). MATERIALS AND METHODS: An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions. RESULTS: Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT. CONCLUSIONS: Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.

Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

BACKGROUND: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. METHODS: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. DISCUSSION: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC. TRIAL REGISTRATION: ClinicalTrials.gov: NCT05673148, registered December 21, 2022.

Flap Reconstruction Results in Longer Overall Treatment Time in Patients Treated with Surgery and Adjuvant Radiotherapy for Carcinoma of the Oral Cavity and Larynx.

OBJECTIVE: There is an inverse relationship between cancer cure and overall treatment time (OTT) in patients treated with surgical resection and radiotherapy (RT). METHODS: OTT was evaluated based on the reconstruction procedure in 420 patients with oral cavity and larynx cancers treated with surgery and RT between 1991 and 2020. RESULTS: With OTT >85 days, the difference between no versus yes flap reconstruction was ~20 percentage points and significant for all comparisons: primary closure (+/- skin graft), 49%, vs. rotation or free flap, 71% (P<0.0001); primary closure (+/- skin graft), 49%, versus free flap without bone, 66% (P=0.0358); and primary closure (+/- skin graft), 49%, versus free flap with bone, 82% (P<0.0001). CONCLUSIONS: The use of flap reconstructions results in substantial increases in OTT. Findings suggest a need to reevaluate current policies regarding the choice of reconstruction and starting RT sooner after surgery.

The room where it happens: addressing diversity, equity, and inclusion in National Clinical Trials Network clinical trial leadership.

Many multicenter randomized clinical trials in oncology are conducted through the National Clinical Trials Network (NCTN), an organization consisting of 5 cooperative groups. These groups are made up of multidisciplinary investigators who work collaboratively to conduct trials that test novel therapies and establish best practice for cancer care. Unfortunately, disparities in clinical trial leadership are evident. To examine the current state of diversity, equity, and inclusion across the NCTN, an independent NCTN Task Force for Diversity in Gastrointestinal Oncology was established in 2021, the efforts of which serve as the platform for this commentary. The task force sought to assess existing data on demographics and policies across NCTN groups. Differences in infrastructure and policies were identified across groups as well as a general lack of data regarding the composition of group membership and leadership. In the context of growing momentum around diversity, equity, and inclusion in cancer research, the National Cancer Institute established the Equity and Inclusion Program, which is working to establish benchmark data regarding diversity of representation within the NCTN groups. Pending these data, additional efforts are recommended to address diversity within the NCTN, including standardizing membership, leadership, and publication processes; ensuring diversity of representation across scientific and steering committees; and providing mentorship and training opportunities for women and individuals from underrepresented groups. Intentional and focused efforts are necessary to ensure diversity in clinical trial leadership and to encourage design of trials that are inclusive and representative of the broad population of patients with cancer in the United States.

Does lymphovascular invasion predict survival in oral cancer? A population-based analysis.

OBJECTIVE: To evaluate lymphovascular invasion as an independent predictor for overall survival in patients with oral cavity squamous cell carcinoma. STUDY DESIGN: Retrospective cohort study. SETTING: Multi-center, population-based facilities reporting to the National Cancer Database registry. METHODS: The database was accessed to collect data on patients with oral cavity squamous cell carcinoma. A multivariate cox proportional hazards model was used to analyze the association between presence of lymphovascular invasion and overall survival. RESULTS: 16,992 patients met inclusion criteria. 3,457 patients had lymphovascular invasion. The mean follow-up was 32 ± 19 months. Lymphovascular invasion predicted reduced 2-year overall survival (relative hazard 1.29, 95% CI: 1.20, 1.38, p < 0.001) and 5-year overall survival (relative hazard 1.30, 95% CI: 1.23, 1.39, p < 0.001). LVI reduced overall survival in patients with squamous cell carcinoma of the oral tongue (HR: 1.27, 95% CI: 1.17, 1.39, p < 0.001), floor of mouth (HR: 1.33, 95% CI: 1.17, 1.52, p < 0.001) and buccal mucosa (HR: 1.44, 95% CI: 1.15, 1.81, p = 0.001). Patients with lymphovascular invasion treated with surgery plus post-operative radiotherapy had significantly improved survival compared to those who underwent surgery alone (relative hazard 1.79, 95% CI: 1.58, 2.03, p < 0.001), and patients treated with surgery + post-operative chemoradiotherapy had improved survival compared to those treated with surgery alone (relative hazard 2.0, 95% CI: 2.26, 1.79, p < 0.001). CONCLUSION: Lymphovascular invasion is an important independent risk factor for decreased overall survival in oral cavity squamous cell carcinoma involving the oral tongue, floor of mouth and buccal mucosa subsites.

Oligometastatic Colorectal Cancer: A Review of Definitions and Patient Selection for Local Therapies.

PURPOSE: Nearly one-third of patients diagnosed with colorectal cancer (CRC) will ultimately develop metastatic disease. While a small percentage of patients can be considered for curative resection, more patients have limited disease that can be considered for local therapy. Challenges remain in defining oligometastatic CRC as well as developing treatment strategies guided by high level evidence. METHODS: In this review, we present the challenges in defining oligometastatic CRC and summarize the current literature on treatment and outcomes of local therapy in patients with metastatic CRC. RESULTS: For patients with liver- and/or lung-confined CRC metastases, surgical resection is the standard of care given the potential for long-term progression-free and overall survival. For patients with liver- or lung-confined disease not amenable to surgical resection, non-surgical local therapies, such as thermal ablation, hepatic arterial infusion pump (HAIP), or stereotactic body radiation therapy (SBRT), should be considered. For patients with more advanced disease, such as lymph node or bony metastases, the role of metastasis-directed therapy is controversial. Emerging data suggests that SBRT to ablate all metastases can improve progression-free and overall survival. CONCLUSION: Multidisciplinary management is critical for patients with metastatic CRC due to the complexity of their cases and the nuanced patient, tumor, biological, and anatomical factors that must be weighed when considering local therapy. High-quality prospective randomized data in CRC are needed to further clarify the role of local ablative therapy in patients with unresectable oligometastatic CRC with ongoing studies including the RESOLUTE trial (ACTRN12621001198819) and the upcoming NCTN ERASur trial (NCT05673148).

Alliance for Clinical Trials in Oncology (Alliance) trial A022101/NRG-GI009: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur).

Background: For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free and overall survival (OS). However, for patients with more advanced mCRC, including those with extrahepatic disease, the efficacy of local therapy is less clear although increasingly being used in clinical practice. Prospective studies to clarify the role of metastatic-directed therapies in patients with mCRC are needed. Methods: The Evaluating Radiation, Ablation, and Surgery (ERASur) A022101/NRG-GI009 trial is a randomized, National Cancer Institute-sponsored phase III study evaluating if the addition of metastatic-directed therapy to standard of care systemic therapy improves OS in patients with newly diagnosed limited mCRC. Eligible patients require a pathologic diagnosis of CRC, have BRAF wild-type and microsatellite stable disease, and have 4 or fewer sites of metastatic disease identified on baseline imaging. Liver-only metastatic disease is not permitted. All metastatic lesions must be amenable to total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR) with SABR required for at least one lesion. Patients without overt disease progression after 16-26 weeks of first-line systemic therapy will be randomized 1:1 to continuation of systemic therapy with or without TAT. The trial activated through the Cancer Trials Support Unit on January 10, 2023. The primary endpoint is OS. Secondary endpoints include event-free survival, adverse events profile, and time to local recurrence with exploratory biomarker analyses. This study requires a total of 346 evaluable patients to provide 80% power with a one-sided alpha of 0.05 to detect an improvement in OS from a median of 26 months in the control arm to 37 months in the experimental arm with a hazard ratio of 0.7. The trial uses a group sequential design with two interim analyses for futility. Discussion: The ERASur trial employs a pragmatic interventional design to test the efficacy and safety of adding multimodality TAT to standard of care systemic therapy in patients with limited mCRC.

Early-stage vocal cord cancer treated with hypofractionated radiotherapy to the larynx with or without concurrent chemotherapy.

BACKGROUND: We report outcomes among patients with T2 and select T3 glottic squamous cell carcinoma (SCC) treated with radiotherapy. METHODS: We reviewed T2 and T3 (only paraglottic space invasion) N0 M0 glottic SCC patients treated with curative-intent hypofractionated larynx radiotherapy, with or without concurrent systemic therapy. RESULTS: Of 71 patients, those who received concurrent chemotherapy (23/71; 32%) had worse prognostic factors, including impaired cord mobility (70% vs. 40%, p = 0.02) and larger median gross tumor volume (3.0 vs. 1.6 cm3 , p = 0.003). Over a median follow-up of 3.8 years, 2-year local control among patients with impaired cord mobility appeared higher for those who received chemotherapy (88% vs. 61%, p = 0.12), but the difference was not statistically significant. Acute and late toxicity rates were not higher among patients who received chemotherapy. CONCLUSIONS: The addition of concurrent platinum-based chemotherapy to hypofractionated larynx radiotherapy among patients with early-stage glottic SCC with impaired cord mobility appears safe and worthy of additional investigation.

Local Therapies in Advanced Colorectal Cancer.

Curative intent surgical resection of colorectal metastases to the liver and lungs in eligible patients results in improved disease control and prolonged overall survival with the potential for cure in a subset of patients. Additional ablative and local therapies for use in the liver, lungs, and other body sites have been developed with emerging data on the utility and toxicity of these treatments. Future studies should focus on identification of appropriate candidates for treatment and determining the optimal modality and timing of treatment accounting for both patient and disease factors.

Retromolar trigone squamous cell carcinoma: A population-based analysis of survival.

OBJECTIVES: To evaluate the difference in overall survival (OS) in patients with retromolar trigone squamous cell carcinoma (RMT SCC) treated with surgery alone versus surgery plus postoperative radiotherapy (PORT) versus surgery plus postoperative chemoradiotherapy (POCRT). MATERIALS AND METHODS: Retrospective cohort study of patients from 1,500 US facilities reporting to the National Cancer Database (NCDB) registry. Participants were adult patients treated with surgery as primary treatment modality for RMT SCC (n = 2,877). Exposures were primary definitive surgery versus surgery + PORT versus surgery + POCRT. Outcomes included OS after diagnosis and treatment of RMT SCC. A multivariate Cox proportional hazards model was constructed to compare survival between the three treatment modalities. Subgroup analysis was performed by T classification and overall staging. RESULTS: There were 1,415 (50%) patients treated with surgery alone, 870 (30%) patients treated with surgery + PORT, and 572 (20%) treated with surgery + POCRT. Treatment with surgery + PORT was associated with improved OS compared to surgery alone (relative hazard: 1.25, 95% CI: 1.01, 1.54, p = 0.042). Patients treated with surgery + POCRT also had improved OS compared with surgery alone (relative hazard: 1.89, 95% CI 1.45, 2.43, p < 0.001). Patients with T3/4 tumors had improved OS when treated with surgery + PORT (relative hazard 1.39, 95% CI: 1.05, 1.84, p = 0.022) or surgery + POCRT (relative hazard 2.27, 95% CI: 1.66, 3.15, p < 0.001). Patients with T1 or T2 disease had no significant difference in survival in both the surgery + PORT (p = 0.331) and surgery + POCRT treatment groups (p = 0.134). Therefore, there was no difference in OS for patients with stage I or II disease treated with surgery + PORT (p = 0.451), nor with surgery + POCRT (p = 0.853). CONCLUSION: Treatment with surgery + PORT +/- chemotherapy appears to be associated with significantly improved OS compared to surgery alone for advanced RMT SCCa.

Sparing the Larynx and Hypopharynx With Radiation Therapy for Squamous Cell Carcinoma of Unknown Primary Site and Predominant Adenopathy in Level IIA.

PURPOSE: There is controversy about the need to target the mucosa of the larynx and hypopharynx during radiation therapy (RT) for squamous cell carcinoma of an unknown primary site (SCCA-UP). By 1997, the policy in our department was to target only the oropharynx and nasopharynx in patients with SCCA-UP metastatic to the level II cervical nodes. The purpose of this study was to report the rate of cancer recurrence in the larynx or hypopharynx using an approach that excluded these areas from the RT target volumes. METHODS AND MATERIALS: The inclusion criteria for this study were RT in our department for SCCA-UP between January 1, 1997, and December 31, 2019; no history of surgery that could disrupt the cervical lymphatics; predominant adenopathy in level IIA; and neck stage N1-2c. We excluded N3 because the incidental dose to the larynx and hypopharynx is usually high in patients with a >6-cm nodal conglomerate. RESULTS: The study population was comprised of 50 patients with a median follow-up after RT of 7.1 years. No patient developed recurrent cancer in a mucosal site (0/50), 2% (1/50) developed a neck recurrence in a high-dose area with synchronous distant metastases, and 2% (1/50) developed distant metastases with no evidence of local or regional recurrence. CONCLUSIONS: When delivering RT for SCCA-UP metastatic predominantly to level IIA, it is not necessary to target the mucosa of the larynx or hypopharynx. The extent to which the incidental RT dose to these areas contributes to cancer control is not evaluated in this study.

Current Role of Radiotherapy in the Management of Oral Cavity Squamous Cell Carcinoma.

STUDY DESIGN: Literature review. OBJECTIVE: To review the current role of radiotherapy (RT) in the management of oral cavity squamous cell carcinoma (SCC). METHODS: Review of selected literature. RESULTS: T1-T2N0 SCCs may be treated with either RT alone or surgery with a high likelihood of cure. The pendulum swung toward surgery with postoperative RT (PORT) added depending on the pathological findings in the mid 1980s. Patients with positive margins, extranodal extension (ENE), and/or 4 or more positive nodes receive concomitant chemotherapy (POCRT). Patients with T3-T4 and/or positive regional nodes are treated with surgery and PORT alone or POCRT. The likelihood of cure is moderate to low depending on extent of disease. The likelihood of major complications ranges from 10% to 30% depending on the method of reconstruction and the aggressiveness of postoperative PORT/POCRT. Patients with very advanced disease are treated with palliative RT, chemotherapy, or supportive care. CONCLUSIONS: The role of RT in the management of oral cavity SCC is primarily in the postoperative setting with palliative RT being reserved for those with very advanced disease where the likelihood of cure is remote.

Curative-intent radiotherapy for glottic carcinoma in situ.

BACKGROUND: The aim of the study was to update our experience treating patients with glottic carcinoma in situ (CIS) with curative radiotherapy (RT). METHODS: Fifty patients received continuous-course RT using once-daily fractionation. Twenty-eight (56%) had recurrent or persistent CIS after resection. Median total dose was 63.0 Gy; median dose per fraction was 2.25 Gy. Median follow-up was 9.6 years for all patients and 8.4 years for survivors. RESULTS: After RT, 5 patients (10%) recurred locally; salvage surgery was performed in 4 (1 refused). Five-year outcomes were as follows: local control, 91%; ultimate local control (including patients successfully salvaged after local recurrence), 100%; ultimate local control with larynx preservation, 93%; local-regional control, 91%; ultimate local-regional control, 100%; distant metastases-free survival, 100%; cause-specific survival, 100%; and overall survival, 81%. No patient experienced a severe complication. CONCLUSION: RT is an excellent treatment for patients with CIS recurrent after transoral excision and those with previously untreated CIS who are unsuitable for partial laryngectomy.

A format for dosimetry comparison studies.

There is no standardized format for presenting and discussing the results of a radiotherapy dosimetry comparison study. The purpose of this report is to describe a format that we have found useful in evaluating plans in our department and in reviewing studies from other groups.

Comparing national practice versus standard guidelines for the use of adjuvant treatment following robotic surgery for oropharyngeal squamous cell carcinoma.

BACKGROUND: Recent historical management of oropharyngeal squamous cell carcinoma typically includes radiotherapy with/without chemotherapy. Novel surgical techniques such as robotic surgery have made primary surgery more frequent; however, postoperative radiotherapy may be recommended. We aimed to assess adherence to guidelines for postoperative therapy following robotic surgery. METHODS: Using the National Cancer Database, we analyzed the frequency of radiotherapy following robotic surgery for cT1-3cN0-2cM0 squamous cell carcinoma of the oropharynx, specifically in the presence of widely accepted indications for postoperative radiotherapy and/or chemotherapy. RESULTS: Approximately two-thirds of patients received radiotherapy after robotic surgery for early-intermediate stage oropharyngeal cancer. One in five patients with an indication for adjuvant radiotherapy and 1/3 with an indication for adjuvant chemotherapy did not receive recommended adjuvant therapy. CONCLUSIONS: A high proportion of patients require radiotherapy after robotic surgery for early-intermediate stage oropharyngeal cancer. Patients with an indication for further adjuvant therapy commonly do not receive it.