Radiotherapy for Atypical Teratoid/Rhabdoid Tumor (ATRT) on the Pediatric Proton/Photon Consortium Registry (PPCR).

PURPOSE: Atypical teratoid/rhabdoid tumors (ATRT) of the central nervous system (CNS) are rare tumors with a poor prognosis and variable use of either focal or craniospinal (CSI) radiotherapy (RT). Outcomes on the prospective Pediatric Proton/Photon Consortium Registry (PPCR) were evaluated according to RT delivered. METHODS: Pediatric patients receiving RT were prospectively enrolled on PPCR to collect initial patient, disease, and treatment factors as well as provide follow-up for patient outcomes. All ATRT patients with evaluable data were included. Kaplan-Meier analyses with log-rank p-values and cox proportional hazards regression were performed. RESULTS: The PPCR ATRT cohort includes 68 evaluable ATRT patients (median age 2.6 years, range 0.71-15.40) from 2012 to 2021. Median follow-up was 40.8 months (range 3.4-107.7). Treatment included surgery (65% initial gross total resection or GTR), chemotherapy (60% with myeloablative therapy including stem cell rescue) and RT. For patients with M0 stage (n = 60), 50 (83%) had focal RT and 10 (17%) had CSI. Among patients with M + stage (n = 8), 3 had focal RT and 5 had CSI. Four-year overall survival (OS, n = 68) was 56% with no differences observed between M0 and M + stage patients (p = 0.848). Local Control (LC) at 4 years did not show a difference for lower primary dose (50-53.9 Gy) compared to ≥ 54 Gy (73.3% vs 74.7%, p = 0.83). For patients with M0 disease, four-year OS for focal RT was 54.6% and for CSI was 60% (Hazard Ratio 1.04, p = 0.95. Four-year event free survival (EFS) among M0 patients for focal RT was 45.6% and for CSI was 60% (Hazard Ratio 0.71, p = 0.519). For all patients, the 4-year OS comparing focal RT with CSI was 54.4% vs 60% respectively (p = 0.944), and the 4-year EFS for focal RT or CSI was 42.8% vs 51.4% respectively (p = 0.610). CONCLUSION: The PPCR ATRT cohort found no differences in outcomes according to receipt of either higher primary dose or larger RT field (CSI). However, most patients were M0 and received focal RT. A lower primary dose (50.4 Gy), regardless of patient age, is appealing for further study as part of multi-modality therapy.

Focal versus craniospinal radiation for disseminated atypical teratoid/rhabdoid tumor following favorable response to systemic therapy.

PURPOSE: Radiotherapy (RT) is associated with improved survival in atypical teratoid/rhabdoid tumor (ATRT); however, optimal RT delivery is unknown. A meta-analysis was conducted for disseminated (M+) ATRT receiving focal or craniospinal radiation (CSI). METHODS: After abstract screening, 25 studies (1995-2020) contained necessary patient, disease, and radiation treatment information (N = 96). All abstract, full text, and data capture were independently double-reviewed. The corresponding author was contacted for cases of insufficient information. Response to pre-radiation chemotherapy (N = 57) was categorized as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD). Univariate and multivariate statistics were performed to investigate survival correlation. Patients with M4 disease were excluded. RESULTS: The 2- and 4-year overall survival (OS) was 63.8% and 45.7%, respectively, with a median follow-up of 2 years (range 0.3-13.5). The median age was 2 years (range 0.2-19.5), and 96% received chemotherapy. On univariate analysis, gross total resection (GTR, p = .0007), pre-radiation chemotherapy response (p < .001), and high-dose chemotherapy with stem cell recuse (HDSCT, p = .002) correlated with survival. On multivariate analysis, pre-radiation chemotherapy response (p = .02) and GTR (p = .012) retained survival significance as compared to a trend for HDSCT (p = .072). Comparisons of focal RT (vs. CSI) and greater than or equal to 5400 cGy primary dose were nonsignificant. Following CR or PR, a statistical trend favored focal radiation (p = .089) over CSI. CONCLUSION: Chemotherapy response prior to RT and GTR correlated with improved survival on multivariate analysis for ATRT M+ receiving RT. No benefit was observed for CSI compared to focal RT among all patients and following favorable chemotherapy response, inviting further study of focal RT for ATRT M+.

The Incorporation of Immunotherapy and Targeted Therapy Into Chemoradiation for Cervical Cancer: A Focused Review.

In 2011 the Food and Drug Administration (FDA) approved anti-vascular endothelial growth factor (VEGF) therapy, bevacizumab, for intractable melanoma. Within the year, immunotherapy modulators inhibiting cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) were approved in addition to programmed death-ligand 1 (PD-L1) antibodies in 2012. Since then, research showing the effectiveness of targeted therapies in a wide range of solid tumors has prompted studies incorporating their inclusion as part of upfront management as well as refractory or relapsed disease. For treatment of cervical cancer, which arises from known virus-driven oncogenic pathways, the incorporation of targeted therapy is a particularly attractive prospect. The current standard of care for locally advanced cervical cancer includes concurrent platinum-based chemotherapy with radiation therapy (CRT) including external beam radiation therapy (EBRT) and brachytherapy. Building upon encouraging results from trials testing bevacizumab or immunotherapy in recurrent cervical cancer, these agents have begun to be incorporated into upfront CRT strategies for prospective study. This article will review background data establishing efficacy of angiogenesis inhibitors and immunotherapy in the treatment of cervical cancer as well as results of prospective studies combining targeted therapies with standard CRT with the aim of improving outcomes. In addition, the role of immunotherapy and radiation on the tumor microenvironment (TME) will be discussed.

Advantages of real-time transabdominal ultrasound guidance in combined interstitial/intracavitary cervical brachytherapy: a case-based review.

Sub-optimal placement of both intracavitary devices and interstitial needles is a relatively common occurrence in cervical brachytherapy, which may reduce the accuracy of dose distribution and contribute to adverse toxicities. To mitigate complications, improve target dose coverage, and verify proper device placement, implants may be placed under real-time image guidance. Traditionally, transrectal ultrasound has been used for needle guidance. However, we have utilized transabdominal ultrasound (TA-US) in our brachytherapy center. The purpose of this pictorial essay was to provide a pictorial description of TA-US technique, present a retrospective review of our preliminary outcomes adopting TA-US into routine practice, and to discuss the advantages of real-time ultrasound image guidance for placement of intrauterine tandem and interstitial needles.

Radiotherapy for stage III non-small-cell lung carcinoma in the elderly (age ≥ 70 years).

BACKGROUND: Elderly patients are underrepresented in trials that establish definitive chemoradiotherapy as the standard of care for inoperable stage III non-small-cell lung carcinoma (NSCLC). This study analyzed radiotherapy treatment delivery and outcomes at our institution according to elderly (≥ 70 years old) or younger (< 70 years) age. METHODS: Records of patients who received radiotherapy for stage III NSCLC between January 1998 and February 2010 were reviewed. Factors analyzed included Eastern Cooperative Oncology Group Performance Status (ECOG PS), weight loss, radiation therapy intent, and chemotherapy administered. RESULTS: A total of 189 patients with stage III NSCLC were analyzed (age range, 28-92 years). Elderly patients (n = 86) were more likely to have ECOG PS ≥ 2 (P < .05) and receive palliative treatment (P < .05). Elderly patients less often received concurrent chemoradiotherapy (P < .05) as well as cisplatin (P < .05). Median survival was 10.3 months for elderly patients compared with 17.2 months for younger patients (P < .05 ). In addition, elderly patients with ECOG PS (P < .05) as well as those who received definitive concurrent chemoradiotherapy (P < .05) had inferior outcomes compared with otherwise similar younger patients. However, on multivariate analysis, elderly age was not associated (P = .428) with increased risk of death, whereas poor ECOG PS (≥ 2) was significant (P < .05). In elderly patients, definitive treatment (P < .05), chemotherapy administration (P < .05), and ECOG PS of 0-1 (P < .05) were associated with improved outcome. CONCLUSIONS: Although elderly patients with stage III NSCLC experience inferior outcomes than younger patients with comparable disease, they are also more likely to receive suboptimal therapy. On multivariate analysis, advanced age was not associated with worse survival, which indicates that appropriately selected elderly patients should receive definitive chemoradiotherapy.

Stereotactic body radiotherapy in patients with stage I non-small-cell lung cancer aged 75 years and older: retrospective results from a multicenter consortium.

BACKGROUND: This study was a retrospective analysis of elderly patients treated with stereotactic body radiotherapy (SBRT) in the setting of a multi-institutional consortium. PATIENTS AND METHODS: Three institutions pooled data on patients aged ≥ 75 years who received SBRT for stage I non-small-cell lung cancer (NSCLC). Forty-seven tumors in 46 patients were analyzed in patients aged 75 to 92 years (median, 82 years). Treatment was delivered during 2007 to 2009, with a median follow-up of 12.4 months. All patients underwent staging positron emission tomography-computed tomography (PET-CT), and 87% of tumors were confirmed by biopsy results. Total doses were 35 to 60 Gy, mainly in 3 to 5 fractions. All tumors were treated using a linear accelerator, with 96% of patients receiving 3-dimensional (3D) conformal RT and 4% undergoing intensity modulated RT (IMRT). RESULTS: At the time of analysis, the local failure rate was 2% (1 of 47). The regional failure rate was 9% (4 of 47). The distant failure rate was 6% (3 of 47). The combined failure rate was 15% (7 of 47) because 1 patient experienced both regional and distant failure. Among 20 tumors with any acute toxicity, there were no ≥ grade 3 toxicities. Pneumonitis (n = 10) grades 1 (n = 3) and 2 (n = 2) was seen in 15% and 10% of patients, respectively; these data were missing for 25% of patients. CONCLUSION: SBRT in patients aged ≥ 75 years with stage I NSCLC proved tolerable, with toxicity rates comparable to those in younger patients. Excellent rates of local, regional, and distant control were achieved at a median follow-up of 12.4 months. This patient population represents a rapidly growing segment of the early lung cancer population, and SBRT appears to be a safe and effective treatment option for patients who are not optimal candidates for surgery.