Locoregional recurrence (LRR) is the predominant pattern of relapse and often the cause of death in patients with retroperitoneal sarcomas (RPS). As a result, reducing LRR is a critical objective for ...RPS patients. However, unlike soft tissue sarcomas (STS) of the superficial trunk and extremity where the benefits of radiation therapy (RT) are well-established, the role of RT in the retroperitoneum remains controversial. Historically, preoperative or postoperative RT, either alone or in combination with intraoperative radiation (IORT), was commonly justified for RPS based on extrapolation from the superficial trunk and extremity STS literature. However, long-awaited results were recently published from the European Organization for Research and Treatment of Cancer (EORTC) STRASS study of preoperative radiotherapy plus surgery versus surgery alone for patients with RPS; there was no statistical difference in the primary endpoint of abdominal recurrence-free survival. However, several subset analyses and study limitations complicate the interpretation of the results. This review explores and contextualizes the body of evidence regarding RT's role in managing RPS.
Abstract Purpose Prophylactic cranial irradiation (PCI) can improve overall survival (OS) and suppress brain metastases (BM) in patients with limited-stage small cell lung cancer (LS-SCLC) after ...complete response to primary therapy. However, PCI can be toxic. We sought to identify characteristics of patients who may not benefit from PCI. Methods We identified 658 patients who received chemoradiotherapy at MD Anderson in 1986–2012; 364 received PCI and 294 did not. Median follow-up time was 21.2 months (range 1.2–240.8 months). Cox proportional hazards regression, competing-risk regression, and Kaplan–Meier analyses were used to identify factors influencing OS and BM. Results PCI reduced risks of death HR 0.73, 95% CI 0.61–0.88, P = 0.001 and BM HR 0.54, 95% CI 0.39–0.76, P < 0.001. Having tumors ⩾5 cm increased the risk of BM HR 1.77, 95% CI 1.22–2.55, P = 0.002 but not death HR 1.16, 95% CI 0.96–1.40, P = 0.114. Among patients ⩾70 years with ⩾5-cm tumors, PCI did not improve OS 2-year rates 39.4% vs 40.9%, P = 0.739. Conclusions PCI remains standard therapy after complete response to chemoradiotherapy for LS-SCLC. However, older patients may be at risk from comorbidity or extracranial disease. Further work is warranted to identify patients who may not benefit from PCI.
Neuroblastoma is a childhood cancer with heterogeneous clinical outcomes. To comprehensively assess the impact of telomere maintenance mechanism (TMM) on clinical outcomes in high-risk neuroblastoma, ...we integrated the C-circle assay a marker for alternative lengthening of telomeres (ALT), TERT mRNA expression by RNA-sequencing, whole-genome/exome sequencing, and clinical covariates in 134 neuroblastoma patient samples at diagnosis. In addition, we assessed TMM in neuroblastoma cell lines (
= 104) and patient-derived xenografts (
= 28). ALT was identified in 23.4% of high-risk neuroblastoma tumors and genomic alterations in
were detected in 60% of ALT tumors; 40% of ALT tumors lacked genomic alterations in known ALT-associated genes. Patients with high-risk neuroblastoma were classified into three subgroups (TERT-high, ALT
, and TERT-low/non-ALT) based on presence of C-circles and TERT mRNA expression (above or below median TERT expression). Event-free survival was similar among TERT-high, ALT
, or TERT-low/non-ALT patients. However, overall survival (OS) for TERT-low/non-ALT patients was significantly higher relative to TERT-high or ALT patients (log-rank test;
< 0.01) independent of current clinical and molecular prognostic markers. Consistent with the observed higher OS in patients with TERT-low/non-ALT tumors, continuous shortening of telomeres and decreasing viability occurred in low TERT-expressing, non-ALT patient-derived high-risk neuroblastoma cell lines. These findings demonstrate that assaying TMM with TERT mRNA expression and C-circles provides precise stratification of high-risk neuroblastoma into three subgroups with substantially different OS: a previously undescribed TERT-low/non-ALT cohort with superior OS (even after relapse) and two cohorts of patients with poor survival that have distinct molecular therapeutic targets. SIGNIFICANCE: These findings assess telomere maintenance mechanisms with TERT mRNA and the ALT DNA biomarker C-circles to stratify neuroblastoma into three groups, with distinct overall survival independent of currently used clinical risk classifiers.
Gynecologic tract melanoma (GTM) is a rare malignancy with historically poor outcomes. The current study examines patterns of care and oncologic outcomes in a large single-institution cohort from the ...contemporary therapeutic era.
Patterns of care and predictors of outcomes were evaluated for all GTM patients without metastatic disease at diagnosis who were treated at our institution between 2009 and 2020 with >6 months of follow-up.
Of the 124 patients included, anatomic subsites were vulvar (n = 82, 66%), vaginal (n = 34, 27%), or cervical (n = 8, 6%). Primary tumor was resected for 85% (n = 106) with surgical nodal evaluation for 60% (n = 75). Systemic therapy, most commonly immune checkpoint inhibitors (ICI, 58% systemic therapy), was used to treat all except one unresectable patient (17/18) and 33% (35/106) of resectable patients. Seven patients received neoadjuvant ICI. Fourteen patients received adjuvant radiation therapy to the pelvis (RT, 13% of those undergoing resection). With a median follow-up of 45 months, 100 patients (81%) recurred. Four-year actuarial outcomes were: 46% local control, 53% nodal control, 36% distant metastasis-free survival, 17% disease-free survival, 49% melanoma-specific survival and 48% overall survival. Mitotic rate > 10/mm
, nodal involvement and non-vulvar anatomic subsite were associated with poor outcomes. Patients treated after 2016 did not have significantly better outcomes than those treated earlier.
Patients with GTM continue to have poor outcomes in the contemporary therapeutic era with particularly notable poor local disease control relative to other mucosal melanoma subtypes. More effective oncologic therapy is needed.
The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease ...burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases.
We performed a retrospective review of patients treated at a tertiary cancer center between 2006 and 2020. Patient disease status at the time of SABR was categorized as either oligorecurrent or oligoprogressive. The Kaplan-Meier method was used to estimate disease outcomes. Uni- and multivariable analyses were conducted using the Cox proportional hazards model.
We identified 70 patients with soft tissue sarcoma treated with SABR to 98 metastatic lung lesions. Local recurrence-free survival after SABR treatment was 83% at 2 years. On univariable analysis, receipt of comprehensive SABR to all sites of pulmonary metastatic disease at the time of treatment was associated with improved progression-free survival (PFS; hazard ratio HR, 0.51 0.29-0.88; P = .02). On multivariable analysis, only having systemic disease controlled at the time of SABR predicted improved PFS (median PFS, 14 vs 4 months; HR, 0.37 0.20-0.69; P = .002) and overall survival (median overall survival, 51 vs 14 months; HR, 0.17 0.08-0.35; P < .0001).
SABR provides durable long-term local control for sarcoma lung metastases. The most important predictor for improved outcomes was systemic disease control. Careful consideration of these factors should help guide decisions in a multidisciplinary setting to appropriately select the optimal candidates for SABR.
Introduction
We investigated outcomes and prognostic factors for patients treated for cutaneous angiosarcoma (CA).
Methods
We conducted a retrospective review of patients treated for CA of the face ...and scalp from 1962 to 2019. All received definitive treatment with surgery, radiation (RT), or a combination (S‐XRT). The Kaplan–Meier method was used to estimate outcomes. Multivariable analyses were conducted using the Cox proportional hazards model.
Results
For the 143 patients evaluated median follow‐up was 33 months. Five‐year LC was 51% and worse in patients with tumors >5 cm, multifocal tumors, those treated pre‐2000, and with single modality therapy (SMT). These remained associated with worse LC on multivariable analysis. The 5‐year disease‐specific survival (DSS) for the cohort was 56%. Tumor size >5 cm, non‐scalp primary site, treatment pre‐2000, and SMT were associated with worse DSS.
Conclusion
Large or multifocal tumors are negative prognostic factors in patients with head and neck CA. S‐XRT improved outcomes.
Purpose of Review
The management of metastatic disease is evolving. As systemic therapies continue to improve, there is increasing recognition that local therapy to distant sites of disease impacts ...outcomes among many histologies, including sarcoma. Various local therapy strategies exist, but radiation therapy (RT) is particularly critical as it provides a non-invasive, yet locally ablative strategy for metastatic management.
Recent Findings
Various delivery techniques including stereotactic body radiation therapy (SBRT) or hypofractionated RT can escalate the biologic dose while avoiding normal tissues in order to reduce tumor burden, provide durable local control, palliate symptoms, potentially prevent further seeding of metastatic lesions, and potentially prolong survival.
Summary
This review summarizes the current state of the literature on the important role of RT for the treatment of metastatic sarcoma organized by the site of metastatic disease. Particularly for patients presenting with oligometastatic or oligoprogressive disease, consolidative RT is an important local therapy strategy to be considered in a multidisciplinary setting.
Background
Management of patients with sentinel lymph node (SLN)-positive melanoma has changed dramatically over the last few years such that completion lymph node dissection (CLND) has become ...uncommon, and many patients receive adjuvant immunotherapy or targeted therapy. This study seeks to characterize patterns and predictors of early recurrence in this setting.
Patients and Methods
All patients with primary cutaneous melanoma undergoing sentinel lymph node biopsy (SLNB) between 3/2016 and 12/2019 were identified. The subset with a positive SLN who did not undergo CLND were examined for further analysis of outcomes and predictors of recurrence.
Results
Overall, 215 patients with SLN-positive melanoma who did not have CLND were identified. Adjuvant systemic therapy was administered to 102 (47%), with 93% of this subset receiving immunotherapy (
n
= 95). Median follow-up from SLNB was 20 months (IQR 12–28.5 months), and 57 patients (27%) recurred during this time. The SLN basin was the most common site of recurrence (
n
= 38, 67% of recurrence), with isolated nodal recurrence being the most common first site of recurrent disease (
n
= 22, 39% of recurrence). On multivariable analysis, lymphovascular invasion (LVI) of the primary tumor, two or more involved nodes, and > 1 mm nodal deposit were independently associated with higher rates of nodal relapse.
Conclusions
Nodal recurrence is a primary driver of early disease relapse for patients with SLN-positive melanoma who do not undergo CLND in the era of effective adjuvant systemic therapy. LVI, ≥ 2 nodes, or > 1 mm nodal disease identifies patients at particularly high risk of nodal relapse.
Neoadjuvant checkpoint inhibition (CPI) has recently demonstrated impressive outcomes in patients with stage 3 cutaneous melanoma. However, the safety, efficacy, and outcome of neoadjuvant CPI in ...patients with mucosal melanoma (MM) are not well studied as MM is a rare melanoma subtype. CPI such as combination nivolumab and ipilimumab achieves response rates of 37-43% in unresectable or metastatic MM but there is limited data regarding the efficacy of these agents in the preoperative setting. We hypothesize that neoadjuvant CPI is a safe and feasible approach for patients with resectable MM.
Under an institutionally approved protocol, we identified adult MM patients with resectable disease who received neoadjuvant anti-PD1 +/- anti-CTLA4 between 2015 to 2019 at our institution. Clinical information include age, gender, presence of nodal involvement or satellitosis, functional status, pre-treatment LDH, tumor mutation status, and treatment data was collected. Outcomes include event free survival (EFS), overall survival (OS), objective response rate (ORR), pathologic response rate (PRR), and grade ≥3 toxicities.
We identified 36 patients. Median age was 62; 58% were female. Seventy-eight percent of patients received anti-PD1 + anti-CTLA4. Node positive disease or satellite lesions was present at the time of treatment initiation in 47% of patients. Primary sites of disease were anorectal (53%), urogenital (25%), head and neck (17%), and esophageal (6%). A minority of patients did not undergo surgery due to complete response (n=3, 8%) and disease progression (n=6, 17%), respectively. With a median follow up of 37.9 months, the median EFS was 9.2 months with 3-year EFS rate of 29%. Median OS had not been reached and 3-year OS rate was 55%. ORR was 47% and PRR was 35%. EFS was significantly higher for patients with objective response and for patients with pathologic response. OS was significantly higher for patients with pathologic response. Grade 3 toxicities were reported in 39% of patients.
Neoadjuvant CPI for resectable MM is a feasible approach with signs of efficacy and an acceptable safety profile. As there is currently no standard approach for resectable MM, this study supports further investigations using neoadjuvant therapy for these patients.
The treatment paradigm for patients with anorectal melanoma eligible for sphincter-sparing excision has evolved over time. This study examines outcomes across a 30-year era in this rare disease with ...poor prognosis.
This retrospective cohort study included all patients with pelvis-confined anorectal melanoma undergoing sphincter-sparing local excision and adjuvant radiation therapy (RT) at our institution between 1989 and 2020. Patterns of care and predictors of outcome were evaluated.
Of the 108 patients included, 92 (85%) presented with clinically uninvolved nodes. For clinically node-negative patients, the sentinel lymph node biopsy rate increased from 18/43 (42%) before 2008 to 38/49 (78%) subsequently and the use of inguinal nodal RT decreased from 33/35 (94%) before 2003 to 1/57 (2%) subsequently. All clinically node-positive patients treated before 2003 received inguinal nodal RT, whereas no node-positive patient treated subsequently received this treatment. Patients treated before 2016 mostly received biochemotherapy, and those treated since 2017 mostly received immune checkpoint inhibitors. With median follow-up of 32 months, 77 patients (71%) recurred. Three-year actuarial outcomes were 84% local control, 64% nodal control, 38% distant metastasis-free survival, 30% disease-free survival, and 51% melanoma-specific survival. Ostomy-free survival at last follow-up was 95%. Factors contributing to outcome were identified. Outcomes for patients treated in the contemporary era (2017+) were not significantly better than those treated earlier.
Sphincter-sparing surgery followed by adjuvant RT results in excellent local control and ostomy-free survival for locally resectable anorectal melanoma. Overall oncologic outcomes continue to be poor, reinforcing the need to identify more effective therapies.
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