A Review of Circulating Tumor DNA as a Biomarker Guide for Total Neoadjuvant Therapy in Patients with Locally Advanced Rectal Cancer.

PURPOSE: Non-operative management of patients with locally advanced rectal cancer (LARC) is emerging as a popular approach for patients that have no evidence of disease following neoadjuvant therapy. However, high rates of local recurrence or distant metastases have highlighted the urgent need for robust biomarker strategies to aid clinical management of these patients. METHODS: This review summarizes recent advances in the utility of cell-free (cf) and circulating tumor (ct) DNA as potential biomarkers to help guide individualized non-operative management strategies for LARC patients receiving neoadjuvant therapy. RESULTS: Liquid biopsies and the detection of cfDNA/ctDNA is an emerging technology with the potential to provide a non-invasive approach to monitor disease response and improve the identification of patients with LARC that would best benefit from non-operative management. CONCLUSIONS: Substantial work is still needed before cfDNA/ctDNA monitoring can be widely adopted in the clinical setting. Studies reviewed herein highlight several areas of opportunity for improving the effectiveness and utility of cfDNA/ctDNA for managing patients with LARC.

Matched-pair Analysis for Survival Endpoints Between Women With Early-stage Uterine Carcinosarcoma and Uterine Serous Carcinoma.

OBJECTIVE: The objective of this study was to compare survival endpoints between women with uterine carcinosarcoma and those with uterine serous carcinoma utilizing matching analysis. METHODS: Patients with stages I to II who underwent hysterectomy at our institution were included in this analysis. Patients with carcinosarcoma were then matched to patients with serous carcinoma based on stage, and adjuvant management received (observation, radiation treatment alone, chemotherapy alone, or combined modality with radiotherapy and chemotherapy. Recurrence-free survival, disease-specific survival, and overall survival were calculated for the 2 groups. RESULTS: A total of 134 women were included (67 women with carcinosarcoma and 67 with serous carcinoma, matched 1:1). There was no statistically significant difference between the 2 groups regarding 5-year recurrence-free survival (59% vs. 62%), disease-specific survival (66% vs. 67%), or overall survival (53% vs. 57%), respectively. The only independent predictor of shorter recurrence-free survival for the entire cohort was the lack of adjuvant combined modality therapy, while lower uterine segment involvement was the only independent predictor for shorter disease-specific survival. Lack of lymph node dissection and lack of adjuvant combined modality therapy were independent predictors of shorter overall survival. DISCUSSION: When matched based on stage and adjuvant treatment, our study suggests that there is no statistically significant difference in survival endpoints between women with early-stage carcinosarcoma and serous carcinoma. Adjuvant combined modality treatment is an independent predictor of longer recurrence-free survival and overall survival.

Elective Nodal Irradiation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns.

BACKGROUND: Traditionally, elective nodal irradiation (ENI) has been used in clinical trials that have established thoracic radiotherapy as instrumental in improving survival for patients with limited-stage small-cell lung cancer (LS-SCLC). However, several reports have suggested that the omission of ENI might be appropriate. Current US practice patterns are unknown regarding ENI for patients with LS-SCLC. MATERIALS AND METHODS: We surveyed US radiation oncologists via an institutional review board-approved questionnaire. The questions covered demographics, treatment recommendations, and self-assessed knowledge of key clinical trials. χ2 and Cochran-Armitage tests were used to evaluate for statistically significant correlations between responses. RESULTS: We received 309 responses. Of the respondents, 21% recommended ENI for N0 LS-SCLC, 29% for N1, and 30% for N2; 64% did not recommend ENI for any of these clinical scenarios. The respondents who recommended ENI were more likely to have been practicing for > 10 years (P < .001), more likely to be in private practice (P = .04), and less likely to be familiar with the ongoing Cancer and Leukemia Group B 30610 trial (P = .04). Almost all respondents (93%) prescribed the same radiation dose to the primary disease and involved lymph nodes. When delivering ENI, 36% prescribed the same dose to the involved and elective nodes, and 64% prescribed a lower dose to the elective nodes. CONCLUSION: Nearly two thirds of respondents did not recommend ENI, which represents a shift in practice. A recent large clinical trial that omitted ENI reported greater overall survival than previously reported and lower-than-expected radiation toxicities, lending further evidence that omitting ENI should be considered a standard treatment strategy.

Radiation Dose and Fractionation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns.

BACKGROUND: Thoracic radiotherapy (TRT) with concurrent chemotherapy is standard for limited-stage small-cell lung cancer (LS-SCLC). However, the optimal dosing and fractionation remain unclear. The National Comprehensive Cancer Network guidelines have recommended either 45 Gy delivered twice daily (BID) or 60 to 70 Gy delivered once daily (QD). However, the current practice patterns among US radiation oncologists are unknown. MATERIALS AND METHODS: We surveyed US radiation oncologists using an institutional review board-approved questionnaire. The questions covered demographic data, self-rated knowledge of key trials, and treatment recommendations. RESULTS: We received 309 responses from radiation oncologists. Of the 309 radiation oncologists, 60% preferred TRT QD and 76% acknowledged QD to be more common in their practice. The respondents in academic settings were more likely to endorse BID treatment by both preference (P = .001) and actual practice (P = .009). The concordance between preferring QD and administering QD in practice was 100%. In contrast, 40% of respondents who preferred BID actually administered QD more often. Also, 15% of physicians would be unwilling to switch from QD to BID and 3% would be unwilling to switch from BID to QD, even on patient request. Most respondents (88%) recommended a dose of 45 Gy for BID treatment. For QD treatment, the division was greater, with 54% recommending 60 Gy, 30% recommending 63 to 66 Gy, and 10% recommending 70 Gy. CONCLUSION: Substantial variation exists in how US radiation oncologists approach TRT dosing and fractionation for LS-SCLC. Three quarters of our respondents reported administering TRT QD most often. The most common doses were 60 Gy QD and 45 Gy BID. The results of the present survey have provided the most up-to-date information on US practice patterns for LS-SCLC.

Preferential use of imaging modalities in staging newly diagnosed rectal cancer: a survey of US radiation oncologists.

BACKGROUND: Accurate staging is crucial for management of patients with newly diagnosed rectal cancer. Endorectal ultrasound (EUS) has been the standard modality in the United States for decades, with magnetic resonance imaging (MRI) now preferred by national guidelines. Positron emission tomography (PET), conversely, is not recommended. The current utilization of imaging modalities by American radiation oncologists in staging newly diagnosed rectal cancer is unknown. METHODS: American radiation oncologists completed an anonymous institutional review board-approved online survey probing their imaging preferences for initial staging of rectal cancer patients. RESULTS: We received 220 responses from American radiation oncologists, with 39% in academic centers and with 45% seeing more than 10 rectal cancer patients per year. Most respondents utilize all three imaging modalities for rectal cancer staging-EUS, MRI and positron emission tomography/computed tomography (PET/CT). Fifty-two percent and 38% of respondents are high utilizers of EUS and MRI, respectively, defined as ordering these tests at least 75% of the time. Forty seven percent were high PET utilizers. The latter was associated with practice in a private setting (P=0.015) and being within 10 years from residency training completion (P<0.01). CONCLUSIONS: Our analysis reveals a dramatic discordance among national guidelines and the practice patterns among American radiation oncologists. More rely on PET for initial staging of rectal cancer patients than on pelvic MRI. Further research needs to determine the most effective imaging work-up of patients with an initial diagnosis of rectal cancer.

Does a fine line exist between regional and metastatic pelvic lymph nodes in rectal cancer-striking discordance between national guidelines and treatment recommendations by US radiation oncologists.

BACKGROUND: Management of rectal cancer with involved lateral pelvic lymph nodes (LPLNs) at the time of diagnosis-the stage we refer institutionally to as Stage 3.5-is controversial. The American Joint Committee on Cancer's 7th edition classifies internal iliac lymph nodes (LNs) as regional (Stage III), but both external and common iliac LNs as metastatic (Stage IV). However, in many Asian countries all LPLNs are considered regional and patients are treated with curative intent, with literature supporting improved outcomes with LPLN dissection. Management patterns of these patients by US radiation oncologists (ROs) are unknown. METHODS: American ROs completed an anonymous institutional review board-approved online questionnaire regarding rectal cancer management. RESULTS: Among the 220 completed responses, 45% treat more than 10 patients annually and 39% work in academia. We found 10.5% and 34.2% recommend biopsy of clinically involved internal and common iliac LNs, respectively. The vast majority of responders-98.6% and 94.5%-treat involved internal and common iliac LNs with curative intent, respectively. Respondents recommend treatment intensification to involved internal iliac LNs by dissection of the nodal basin (88.2%) and radiation therapy (RT) boost (59.1%), and treatment intensification to involved common iliac LNs by LN dissection (76.4%) and RT boost (63.6%). CONCLUSIONS: Our analysis reveals that the vast majority of US ROs approach patients with involved LPLNs, both regional (internal iliac) and metastatic (common iliac), with curative intent. They recommend treatment intensification with surgical resection and/or RT boost to involved nodes. Prospective clinical trials need to determine the appropriate management of patients with Stage 3.5 rectal cancer.

Timing of Thoracic Radiation Therapy With Chemotherapy in Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Current Practice Patterns.

INTRODUCTION: For limited-stage small-cell lung cancer (LS-SCLC), National Comprehensive Cancer Network guidelines recommend that thoracic radiotherapy (TRT) be delivered concurrently with chemotherapy and early in the regimen, with cycle 1 or 2. Evidence is conflicting regarding the benefit of early timing of TRT. A Korean randomized trial did not see a survival difference between early (cycle 1) and late (cycle 3) TRT. Current United States (US) practice patterns are unknown. MATERIALS AND METHODS: We surveyed US radiation oncologists using an institutional review board-approved online questionnaire. Questions covered treatment recommendations, self-rated knowledge of trials, and demographics. RESULTS: We received 309 responses from radiation oncologists. Ninety-eight percent recommend concurrent chemoradiotherapy over sequential. Seventy-one percent recommend starting TRT in cycle 1 of chemotherapy, and 25% recommend starting in cycle 2. In actual practice, TRT is started most commonly in cycle 2 (48%) and cycle 1 (44%). One-half of respondents (54%) believe starting in cycle 1 improves survival compared with starting in cycle 3. Knowledge of the Korean trial was associated with flexibility in delaying TRT to cycle 2 or 3 (P = .02). Over one-third (38%) treat based on pre-chemotherapy volume. CONCLUSION: US radiation oncologists strongly align with National Comprehensive Cancer Network guidelines, which recommend early concurrent chemoradiotherapy. Nearly three-quarters of respondents prefer starting TRT with cycle 1 of chemotherapy. However, knowledge of a trial supporting a later start was associated with flexibility in delaying TRT. Treating based on pre-chemotherapy volume-endorsed by over one-third of respondents-may add unnecessary toxicity. This survey can inform development of future trials.

Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer: Survey of US Radiation Oncologists on Current Practice Patterns.

PURPOSE: Prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) is considered the standard of care. Meta-analysis of 7 clinical trials indicates a survival benefit to PCI, but all of these trials were conducted in the pre-magnetic resonance imaging (MRI) era. Therefore, routine brain imaging with MRI before PCI-as recommended by National Comprehensive Cancer Network guidelines-is not directly supported by the evidence. Current US practice patterns for patients with LS-SCLC are unknown. MATERIALS AND METHODS: We surveyed practicing US radiation oncologists via an institutional review board-approved online questionnaire. Questions covered demographic information and treatment recommendations for LS-SCLC. RESULTS: We received 309 responses from US radiation oncologists. Ninety-eight percent recommended PCI for patients with LS-SCLC, 96% obtained brain MRI before PCI, 33% obtained serial brain imaging with MRI after PCI to detect new metastases, and 35% recommended memantine for patients undergoing PCI. Recommending memantine was associated with fewer years of practice (P < .001), fewer lung cancer patients treated per year (P = .045), and fewer LS-SCLC patients treated per year (P = .024). CONCLUSION: Almost all responding radiation oncologists recommended PCI and pre-PCI brain MRI for LS-SCLC patients with disease responsive to initial therapy. Only a third of respondents followed these patients with serial brain MRI. Approximately one third provided memantine therapy to try to limit neurocognitive effects of PCI. Further research is warranted to determine the best treatment for patients with LS-SCLC. This survey can inform the development of future trials that depend on participation from radiation oncologists.

Survey results of US radiation oncology providers' contextual engagement of watch-and-wait beliefs after a complete clinical response to chemoradiation in patients with local rectal cancer.

BACKGROUND: Watchful waiting in rectal cancer patients with a complete clinical response (cCR) to chemoradiation therapy (CRT) forgo upfront resection has been proposed. Growing evidence suggests that a watch-and-wait approach using resection for salvage of local recurrence may improve quality of life without jeopardizing outcomes. The current acceptance of watch-and-wait by US radiation oncologists (ROs) is unknown. METHODS: US ROs completed our IRB-approved anonymous e-survey regarding non-surgical management of patients who achieved a cCR to neoadjuvant CRT. Self-ranked knowledge of the OnCoRe Project-UK prospective observational study of watch-and-wait-was tested for its association with ROs' attitudes using the Chi-squared or Fisher's test, as indicated. Supporters of observation are self-identified. RESULTS: Of the 220 respondents, 48% (n=106) of respondents support watchful waiting and 48% claimed familiarity with the OnCoRe Project. Respondents supporting observation were more likely to be familiar with the publication (P=0.029). Among watch-and-wait supporters, 59% (n=62) felt comfortable discussing this approach and 41% preferred the conversation be initiated by other specialists. There was no association between comfort level in discussing watch-and-wait and familiarity with the OnCoRe Project. ROs treating more than 10 locally advanced rectal cancer (LARC) patients annually felt more comfortable discussing watch-and-wait (P=0.015) compared to ROs seeing fewer patients. CONCLUSIONS: Almost half of surveyed US ROs support watch-and-wait, though many do not feel comfortable discussing this paradigm with patients. Knowledge of the OnCoRe Project is associated with support of watch-and-wait, yet not comfort level in leading the discussion. These results inform provider attitudes toward future clinical study participation.