Predictors of Pathologic Response After Total Neoadjuvant Therapy in Patients With Rectal Adenocarcinoma: A National Cancer Database Analysis.

Purpose/objectives Induction chemotherapy followed by chemoradiation and surgical resection in rectal cancer, known as total neoadjuvant therapy (TNT), is associated with improved pathologic complete response (pCR) rates. The National Cancer Database was utilized to identify factors associated with pCR and survival following treatment with TNT compared to standard neoadjuvant chemoradiation (nCRT). Materials/methods The National Cancer Database was queried from 2004 to 2015 for patients with locally advanced, non-metastatic rectal cancer. We identified 16,299 patients receiving neoadjuvant chemotherapy and radiation followed by definitive surgical resection. Patients were stratified by treatment received, either TNT (n=350) or nCRT (n=15,949). Multivariate binomial regression analysis and propensity matching were used to evaluate predictors of pCR. Kaplan-Meier and Cox multivariate analysis of survival were performed. Results Median follow-up was 38 months vs 53 months in the TNT vs nCRT groups, respectively. There were more patients with T4 or node-positive disease in the TNT group. There was a trend towards improved pCR in the TNT group (p=0.053). Patients achieving pCR had improved 5-year overall survival (OS) of 85.1%. The 5-year OS was not improved for TNT (76.2%) over nCRT (69.9%) (p=0.19). Pelvic nodal pCR was significantly higher in the TNT group (72%). When stratified by clinical stage, patients with cT3 (p=0.038) or cN1 (p=0.049) disease had improved OS with TNT. Conclusions Compared to nCRT, TNT is correlated with higher rates of complete pelvic nodal clearance in patients with locally advanced rectal adenocarcinoma. The use of TNT showed improved survival in patients with cT3 and cN1 disease, indicating a potential benefit for patients with less advanced disease.

Radiographic and Tumor Biomarker Response to Radiotherapy for Recurrent Granulosa Cell Tumor of the Ovary.

Granulosa cell tumors (GCTs) of the ovary are rare, comprising less than 5% of all malignant ovarian neoplasms. While generally considered indolent, GCTs have a tendency for metastasis and delayed relapse, with recurrence developing in 20%-50%. Recurrent or metastatic disease is associated with aggressive behavior and a poor prognosis, as nearly 70% of patients developing recurrence will eventually succumb to their disease. The optimal management of relapsed disease is controversial. Initial salvage therapy typically involves surgical debulking followed by cisplatin-based chemotherapy. Unfortunately, tumor responses are durable for less than half of patients treated with this regimen. Radiation therapy is an attractive option for providing rapid palliation and improving local control without the morbidity of additional surgery or chemotherapy. Here we describe a case of multiply recurrent, rapidly growing intraperitoneal GCT refractory to repeated surgical debulking and several lines of systemic therapy. The patient was treated with two courses of palliative radiotherapy and achieved rapid symptomatic relief, achieving over a 90% reduction in tumor volume. Serum concentration of inhibin B, often inappropriately elevated in patients with GCT, decreased by 98% following irradiation with no interim systemic therapy. At one-year follow-up, the patient has no evidence of radiographic or biochemical recurrence.

Patterns of palliative care consultation among patients with brain metastasis: an opportunity for radiation oncologists to facilitate earlier referral.

BACKGROUND: Early palliative care (PC) physician involvement alongside standard oncologic care has been recommended by the American Society of Clinical Oncology (ASCO) guidelines for all advanced cancer patients, although adherence to these guidelines is variable. Radiation oncologists (ROs) could help facilitate early PC referral for patients treated with palliative radiation, particularly those with brain metastasis (BRM), and the aim of this study was to evaluate the circumstances of PC referral at our institution to better understand the multidisciplinary approaches to facilitate it. METHODS: Patients diagnosed with BRM from non-small cell lung cancer (NSCLC) from 2012 to 2018 whose primary RO and MO were at our institution were reviewed. Overall survival and time to PC consultation from the first oncologic visit following BRM diagnosis was determined using the KaplanMeier method. Mann-Whitney U and Chi-Squared assessed for predictive factors for shorter time to PC consultation. For these factors, the overall survival, rate of PC consultation, and PC setting was used to determine utilization of early PC. RESULTS: Among 103 eligible patients, only 48% underwent a PC consultation in their lifetime, with the initial evaluation being as an outpatient for 37%, and within 1 month of death for 35%. Median survival from BRM diagnosis was 9.0 months. The median time from oncologic appointment to PC referral was 2.8 months, and from initial PC consultation to death was 1.6 months. Only more recent BRM diagnosis (2016-2018 vs. 2012-2015) was associated with shorter time to PC consultation (1.0 vs. 5.6 months, P=0.013), increased PC consult rate (60% vs. 42%, P=0.105), and increased outpatient PC consultation (56% vs. 26%, P=0.037). CONCLUSIONS: The majority of patients did not undergo early PC consultation, though utilization has improved over time. As ROs are commonly involved in BRM management, they may be in a position to proactively support early PC consultations in this patient population.

Impact of Systemic Therapy Type and Timing on Intracranial Tumor Control in Patients with Brain Metastasis from Non-Small-Cell Lung Cancer Treated With Stereotactic Radiosurgery.

OBJECTIVE: Stereotactic radiosurgery (SRS) can effectively control brain metastasis (BRM) from non-small-cell lung cancer (NSCLC), although intracranial recurrence from untreated micrometastatic tumor deposits is common without whole-brain radiotherapy. Our goal was to determine if immunotherapy improves distant intracranial progression-free survival (DI-PFS) compared with other systemic therapies in patients treated with SRS. METHODS: All patients from 2011 to 2019 treated with SRS without previous whole-brain radiotherapy for NSCLC BRM were reviewed. DI-PFS for the entire cohort, and subgroups of patients, was estimated and compared using the Kaplan-Meier/log-rank method. RESULTS: One hundred and thirty-six SRS sessions used to treat 99 patients were reviewed; 98 (72%) for previously untreated BRM and 38 (28%) for recurrent BRM. 35% received immunotherapy (77% concurrent with SRS), 46% received chemotherapy (75% concurrent), and 18% received epidermal growth factor receptor/anaplastic lymphoma kinase (ALK) targeted therapy (85% concurrent). At median follow-up of 13.7 months, 49% developed distant intracranial recurrence. One-year DI-PFS was improved with any use of immunotherapy (58% vs. 39%; P = 0.03) and concurrent immunotherapy versus chemotherapy or targeted therapy (67% vs. 37% vs. 39%, respectively; P = 0.01). In the immunotherapy cohort, 1-year DI-PFS was improved for programmed death-ligand 1 expression ≥50% versus 1%-49% versus 0% (80% vs. 49% vs. 19%, respectively; P < 0.01), and Lung Immune Prognostic Index 0-1 versus 2 (63% vs. 34%; P = 0.03). CONCLUSIONS: Immunotherapy concurrent with SRS, particularly in patients with high programmed death-ligand 1 expression or low Lung Immune Prognostic Index, is associated with improved DI-PFS and no increased risk of radiation necrosis compared with other systemic therapies for NSCLC.

Tumor Cavity Recurrence after Stereotactic Radiosurgery of Surgically Resected Brain Metastases: Implication of Deviations from Contouring Guidelines.

BACKGROUND: Significant heterogeneity exists in target volumes for postoperative stereotactic radiosurgery (SRS) for brain metastases. A set of contouring guidelines was recently published, and we investigated the impact of deviations. METHODS: Patients (n = 41) undergoing single-fraction Gamma Knife SRS following surgical resection of brain metastases from 2011 to 2017 were retrospectively reviewed. SRS included the entire contrast-enhancing cavity with heterogeneity in inclusion of the surgical tract and no routine margin along the dura or clinical target volume margin. Follow-up MR imaging was fused with SRS plans to assess patterns of failure. RESULTS: The median follow-up was 11.1 months with a median prescription of 18 Gy. There were 5 local failures: infield (n = 3, 60%), surgical tract (n = 1, 20%), and marginal > 5 mm from the resection cavity (n = 1, 20%). No marginal failures < 5 mm or dural margin failures were noted. For deep lesions (n = 13), 62% (n = 8) had the entire tract covered. The only tract recurrence was in a deep lesion without coverage of the surgical tract (n = 1/5). CONCLUSION: In this small preliminary experience, despite no routine inclusion of the dural tract or bone flap, no failures were noted in these locations. Omission of the surgical tract in deep lesions may increase failure rates.