Squamous cell carcinoma of the bladder: Demographics and outcomes associated with surgery and radiotherapy.

BACKGROUND AND OBJECTIVES: Squamous cell carcinoma of the bladder (SCCB) is a rare disease composing 2%-5% of all bladder cancers with no consensus regarding treatment. The present study aims to analyze the outcomes of established treatments, namely chemotherapy, radiation, and surgery, to guide clinical decision-making for patients with non-schistosomal SCCB. METHODS: Patients with bladder SCC diagnosed between 2000 and 2018 were reviewed utilizing data from the Surveillance, Epidemiology, and End Results Registry (SEER) program. RESULTS: A total of 5653 patients with SCCB were identified; median survival was 13 months and was significantly decreased in patients treated with chemotherapy or radiation (median survival of 9 or 12 months, respectively). Patients treated with both surgery and radiotherapy saw a decreased 5 year overall survival (OS) of 14%, compared to 35% for those treated with surgery alone (p < 0.01). Furthermore, patients treated with surgery, chemotherapy, and radiotherapy saw a decreased 5 year OS of 20%, compared with 25% for those that received surgery and chemotherapy only (p < 0.01). Finally, surgical intervention provided an increased 5 year OS for patients with locoregional disease only; those with distant disease saw no increase in 5 year OS (p < 0.01). CONCLUSIONS: Based on this study's analysis, radical surgery may be the most effective treatment for this disease.

Squamous cell carcinoma of the colon: evaluation of treatment modalities and survival.

BACKGROUND: Squamous cell carcinoma of the colon (CSCC) is a rare subtype of colon cancer. This study aimed to evaluate treatment strategies and overall survival (OS). METHODS: Using the Surveillance, Epidemiology, and End Results program database from 2008 to 2019, patients aged 18 years with CSCC were identified. Treatment strategies and OS were summarized using the Kaplan-Meier analysis and the log-rank test. Adjusted Cox proportional hazards regression model ratios were calculated to evaluate the effect of confounding variables. RESULTS: After exclusions, 153 patients met the inclusion criteria. The most common treatment modalities included surgery alone (52.1%), surgery and adjuvant chemotherapy (12.9%), and no treatment (26.4%). Kaplan-Meier analysis revealed that patients who underwent surgery and adjuvant chemotherapy had significant improvements in OS (log-rank P = .002). Cox regression analysis revealed tumor grade (hazard ratio [HR], 2.12; 95% CI, 1.17-3.86) and receipt of chemotherapy (HR, 2.66; 95% CI, 1.23-5.76) as the only factors associated with improvements in OS. CONCLUSION: Patients who underwent surgery in combination with chemotherapy had better OS than those who underwent surgery alone. Tumor grade and receipt of chemotherapy were independently associated with OS.

Radioligand therapy (RLT) used to treat cardiac metastasis of pancreatic neuroendocrine tumor.

Radioligand Therapy (RLT) in the form of [177Lu] Lu-DOTA-TATE (Lutathera®) is a promising treatment for pancreatic neuroendocrine tumors (pNETs) with cardiac metastasis. We present a patient treated with [177Lu] Lu-DOTA-TATE that showed shrinkage of metastasis after four treatments at 7.4 GBq every 8 weeks.

Primary squamous cell carcinoma of the pancreas: an update on a rare neoplasm from the SEER database.

Introduction: Pancreatic squamous cell carcinoma is a rare type of pancreatic cancer of ductal origin, composing an estimated 0.5 - 5% of pancreatic ductal malignancies. As a result, epidemiology, treatment options, and associated outcomes are poorly understood and understudied. Our aim was two-fold: to evaluate demographic trends and analyze overall survival (OS) associated with different treatment modalities for this rare malignancy. Methods: Patients with pancreatic squamous cell carcinoma diagnosed between 1992 and 2019 were eligible and reviewed utilizing the Surveillance, Epidemiology, and End Results Registry (SEER) database. Data was analyzed using SPSS and python packages lifelines and pandas. Variables of interest included stage at diagnosis as well as the receipt of surgery, radiotherapy, and/or chemotherapy. Five-year OS curves were analyzed using Kaplan-Meier probability stratified by treatment modality. Results: Of 342 cases of pancreatic squamous cell carcinoma, 170 (49.7%) were females and 172 (50.3%) were males. 72 (21.1%) of patients received radiotherapy, 123 (35.9%) patients received chemotherapy, and 47 (13.7%) received surgery. Patients who were diagnosed under the age of 50 had prolonged survival time compared to those diagnosed over the age of 50 (12 vs 8 months, respectively, p < 0.001). This trend was evident despite the lack of a significant association between age at diagnosis and presence of metastases (p = 0.524). The median OS was 3 months for the entire cohort and there was a significant difference in median survival time noted across treatment modalities: OS was prolonged in those receiving surgery compared to those receiving chemotherapy or radiotherapy alone (30 vs 2 months, respectively, (p<0.001)). Receipt of radiotherapy was not associated with a significant difference in OS compared to those who did not receive radiotherapy. Conclusion: Pancreatic squamous cell carcinoma is a rare subtype of pancreatic cancer and typically portends a poor prognosis. As demonstrated by our study, surgery offers prolonged overall survival compared to other treatment modalities. Age at diagnosis and presence of metastatic disease are also important prognostic factors likely related to patients' ability to tolerate surgery or physician willingness to offer surgery. Given the importance of surgery on outcomes, it may be reasonable to offer it in the oligometastatic setting in patients who are otherwise a good candidate. Future research on larger cohorts is warranted to investigate the role that modality selection plays in overall survival rates in this understudied malignancy.

Opportunity Costs of Surgical Resection and Perioperative Chemotherapy for Locoregional Pancreatic Adenocarcinoma.

PURPOSE: Given the perioperative morbidity and intensity of multimodality treatment, patients with resected pancreatic ductal adenocarcinoma (PDAC) spend a substantial amount of time in clinical care. The primary aim was to determine total time spent in multimodality care for patients with locoregional PDAC. METHODS: A cohort study of all patients who underwent curative-intent resection for PDAC at a single-institution, tertiary care center was performed (2015-2019). Exact times for all relevant visits were abstracted from the primary medical record, and travel time was calculated. Care time was divided into preoperative, surgical, radiation, and systemic therapy phases of care. Primary outcome measures were the percentage of total survival time (TST) and percentage of overall survival (OS) days spent in receipt of care. RESULTS: One hundred seven patients were included. Patients spent a median of 5.0% (interquartile range [IQR] 2.4%-10.1%) of TST and 11.0% (IQR, 5.7%-20.4%) of OS days in receipt of clinical care. Preoperative, surgical, radiation, and systemic therapy phases of care comprised a median of 0.9% (IQR, 0.4%-2.2%), 3.0% (IQR, 1.9%-6.8%), 4.4% (IQR, 3.6%-6.3%), and 10.0% (IQR, 6.2%-14.1%) of OS days. The median per-visit travel time was 60 minutes (IQR, 32-120), and the median cumulative travel time was 22.0 hours (IQR, 12.0-51.5). 12.1% (n = 13) and 7.8% (n = 4) of patients spent > 10% of TST in receipt of surgical and systemic therapy care, respectively. CONCLUSION: Patients with locoregional pancreatic cancer spend a considerable percentage of their survival time in receipt of oncologic care. Further research to determine predictors of increased time burden is warranted to better inform shared decision making.

Inter-fractional variation of markers and applicators in single-implant high-dose-rate interstitial brachytherapy for gynecologic malignancies.

PURPOSE: Implanted fiducial markers are a commonly used tool in delineating the CTV in high-dose-rate interstitial brachytherapy (HDR-ISBT) for gynecologic malignancy, but their reliability in gynacological sites is not well understood. These markers and interstitial applicators can experience interfractional motion due to organ swelling or other anatomical changes. The purpose of this study was to evaluate the spatial variation of these features. METHODS AND MATERIALS: The spatial positions of 50 implanted markers and 202 needles were tracked in 15 patients treated over 70 fractions of HDR brachytherapy. Marker and/or needle coordinates were extracted from CT images with contours and dose distributions. Automated analysis determined marker self-consistency and displacements between various elements of the implant. RESULTS: From start to end fraction, the relative positions of the markers experienced an average magnitude displacement of 4.5 ± 3.0 mm while the average displacement of the applicator tips was 11 ± 8 mm, relative to their respective centers of mass (CM). CONCLUSIONS: Markers implanted lateral and superior to the CTV experience greater drift than other implant locations.

Volume of Disease as a Predictor for Clinical Outcomes in Patients With Melanoma Brain Metastases Treated With Stereotactic Radiosurgery and Immune Checkpoint Therapy.

PURPOSE/OBJECTIVES: Clinical trials of anti-Programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein (CTLA-4) therapies have demonstrated a clinical benefit with low rates of neurologic adverse events in patients with melanoma brain metastases (MBMs). While the combined effect of these immunotherapies (ITs) and stereotactic radiosurgery (SRS) has yielded impressive results with regard to local control (LC) and overall survival (OS), it has also been associated with increased rates of radiation necrosis (RN) compared to historical series of SRS alone. We retrospectively reviewed patients treated with IT in combination with SRS to report on predictors of clinical outcomes. MATERIALS AND METHODS: Patients were included if they had MBMs treated with SRS within 1 year of receiving anti-PD-1 and/or CTLA-4 therapy. Clinical outcomes including OS, LC, intracranial death (ID), and RN were correlated with type and timing of IT with SRS, radiation dose, total volume, and size and number of lesions treated. RESULTS: Twenty-nine patients with 171 MBMs were treated between May 2012 and May 2018. Patients had a median of 5 lesions treated (median volume of 6.5 cm3) over a median of 2 courses of SRS. The median dose was 21 Gy. Most patients were treated with ipilimumab (n = 13) or nivolumab-ipilimumab (n = 10). Most patients underwent SRS concurrently or within 3 months of receiving immunotherapy (n = 21). Two-year OS and LC were 54.4% and 85.5%, respectively. In addition, 14% of patients developed RN; however, only 4.7% of the total treated lesions developed RN. The median time to development of RN was 9.5 months. Patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID (p = 0.05) and RN (p = 0.03). There was no difference in OS, ID, or RN with regard to type of IT, timing of SRS and IT, number of SRS courses, SRS dose, or number of cumulative lesions treated. CONCLUSIONS: In our series, patients treated with SRS and IT for MBMs had excellent rates of OS and LC; however, patients with an aggregate tumor volume >6.5 cm3 were found to be at increased risk of ID and RN. Given the efficacy of combined anti-PD-1/CTLA-4 therapy for MBM management, further study of optimal selection criteria for the addition of SRS is warranted.

A Prospective Study of Early Radiation Associated Cardiac Toxicity Following Neoadjuvant Chemoradiation for Distal Esophageal Cancer.

Purpose: This study aimed to prospectively evaluate the early effects of radiation on cardiac structure and function following neoadjuvant chemoradiation for distal esophageal cancer. Methods and Materials: Patients with non-metastatic esophageal cancer who were suitable for tri-modality therapy with concurrent chemoradiotherapy followed by esophagectomy were enrolled. Cardiac magnetic resonance imaging (CMR) was obtained at baseline and 3-5 months following completion of chemoradiation. Standardized myocardial segmentation was used to identify regions on post-treatment CMR with new T2 signal or late gadolinium enhancement (LGE). Pre and post-treatment cardiac function was assessed with quantitative end points including left ventricle end-systolic volume (LSESV). Serum biomarkers of cardiac damage including troponin I, CRP, and BNP were collected at baseline and time of follow-up CMR. Results: A total of 11 patients were enrolled from 2016 to 2018. Patients had clinical stage T2 (18%) and T3 (82%) disease with clinical N0 (27%) and N1 (73%) nodal stage. All patients completed baseline CMR and completed chemoradiotherapy. One patient did not complete follow-up CMR or serum biomarkers and was excluded from the analysis. The median time from completion of chemoradiation to follow-up CMR was 3.9 months. Three out of 10 patients (30%) developed new structural findings of myocardial fibrosis and/or reversible ischemia involving the basal and mid-inferior and inferoseptal walls. In these three patients, the LVESV was significantly increased from baseline following radiation. There were no differences in other quantitative end points or serum biomarkers between the patients with myocardial damage and those without. Conclusions: Our study is the first to our knowledge to prospectively demonstrate radiation associated structural and functional heart damage as early as 3 months following neoadjuvant chemoradiation for distal esophageal cancer. Given the early onset of this subclinical heart damage, strategies should be developed to identify patients at risk for future clinically significant heart toxicity.

Five-Fraction Stereotactic Body Radiation Therapy (SBRT) and Chemotherapy for the Local Management of Metastatic Pancreatic Cancer.

BACKGROUND: The majority of patients with pancreatic cancer are diagnosed with metastatic disease at presentation. Nevertheless, local progression is responsible for up to 30% of deaths and can lead to significant morbidity. As a consequence, further exploration of effective methods of local control and palliation is essential. Stereotactic body radiation therapy (SBRT) is a widely utilized technique for the treatment of localized pancreatic cancer. Here, we report our experience with SBRT and chemotherapy for the local treatment of the metastatic patient population. METHODS: This single institution retrospective review analyzed 20 patients with pathologically diagnosed metastatic adenocarcinoma of the pancreas. All patients underwent fiducial placement under endoscopic ultrasound (EUS) guidance. SBRT was delivered in five fractions to a total dose of 25 to 30 Gy. Patients received concurrent (given within 1 week of the start of SBRT) or sequential chemotherapy. Local tumor control was evaluated using Response Evaluation Criteria in Solid Tumors. Toxicity was graded using Common Terminology Criteria for Adverse Events version 4.03. Local control and overall survival were reported using the Kaplan-Meier method. RESULTS: Patient median age was 64 years, and the median pre-treatment Eastern Cooperative Oncology Group performance status was 1. All patients received chemotherapy and half of the patients (10 of 20) received concurrent chemotherapy with folinic acid, fluorouracil, and oxaliplatin or fluorouracil, leucovorin, irinotecan, and oxaliplatin. Nearly all patients (19 of 20) received post-SBRT chemotherapy. Median time from pathological diagnosis to SBRT was 3.9 months. The twelve-month local control and overall survival were 43 and 53%, respectively. However, in patients with planning target volume (PTV) targets smaller than the population median, the 12-month local control was 78%. Median time to local progression (17.8 vs. 3.0 months, p = 0.02) and overall survival (24.9 vs. 8.8, p = 0.001) were also significantly improved in this smaller PTV cohort. Though not statistically significant, there was a trend towards improvement in local control (17.8 vs. 4.3 months, p = 0.17) and overall survival (16.7 vs. 9.7 months, p = 0.087) for those who received concurrent versus sequential chemotherapy, respectively. Lastly, there were no reported grade 3-5 late toxicities. CONCLUSIONS: As systemic therapies improve, the local management of pancreatic cancer will become increasingly important. Here, we report significantly improved local control with SBRT of smaller PTV tumors with concurrent chemotherapy. Five-fraction SBRT offers a quick and effective modality of local tumor control with minimal toxicity in the metastatic pancreatic cancer population.