Risk-Tailoring Radiotherapy for Endometrial Cancer: A Narrative Review.

Endometrial cancer is the most common gynecologic cancer in the United States and it contributes to the second most gynecologic cancer-related deaths. With upfront surgery, the specific characteristics of both the patient and tumor allow for risk-tailored treatment algorithms including adjuvant radiotherapy and systemic therapy. In this narrative review, we discuss the current radiation treatment paradigm for endometrial cancer with an emphasis on various radiotherapy modalities, techniques, and dosing regimens. We then elaborate on how to tailor radiotherapy treatment courses in combination with other cancer-directed treatments, including chemotherapy and immunotherapy. In conclusion, this review summarizes ongoing research that aims to further individualize radiotherapy regimens for individuals in an attempt to improve patient outcomes.

The effects of radiation therapy on the heart: implications for management.

Chemotherapy, radiotherapy, and surgery constitute the three primary modalities employed in the treatment of patients with cancer. Radiotherapy, in particular, is a mainstay of treatment for patients with cancers of the breast, esophagus, lung, and lymph nodes. Prior studies have shown, however, that radiotherapy can impact the heart. Radiation exposure, in fact, can lead to pathophysiological changes that may result in short- and long-term radiation-induced cardiac toxicities. Such toxicities can cause substantial morbidity and may manifest clinically in the weeks to years after the completion of treatment. As a result, in both modern clinical practice and clinical trials, the heart has been recognized as an organ-at-risk, and radiotherapy treatment plans seek to minimize the dose that it receives. In this review, we focus on the impacts of radiotherapy on underlying cardiac risk factors, the pathophysiology of radiotherapy-induced cardiac changes, and the clinical impacts of radiotherapy on the heart. Due to the location of the heart, we focus primarily on patients who have received radiotherapy for cancers of the breast, esophagus, lung, and lymph nodes, and those who have received cardiac-directed therapy. We then elaborate on the ongoing attempts to further lower the doses delivered to the heart during therapeutic courses of radiation.

Immune Escape in Glioblastoma: Mechanisms of Action and Implications for Immune Checkpoint Inhibitors and CAR T-Cell Therapy.

Glioblastoma, the most common primary brain cancer in adults, is characterized by a poor prognosis and resistance to standard treatments. The advent of immunotherapy has revolutionized the treatment of several cancers in recent years but has failed to demonstrate benefit in patients with glioblastoma. Understanding the mechanisms by which glioblastoma exerts tumor-mediated immune suppression in both the tumor microenvironment and the systemic immune landscape is a critical step towards developing effective immunotherapeutic strategies. In this review, we discuss the current understanding of immune escape mechanisms in glioblastoma that compromise the efficacy of immunotherapies, with an emphasis on immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy. In parallel, we review data from preclinical studies that have identified additional therapeutic targets that may enhance overall treatment efficacy in glioblastoma when administered alongside existing immunotherapies.

Healthcare Disparities and Outcomes of Cancer Patients in a Community Setting from a COVID-19 Epicenter.

There have been numerous studies demonstrating how cancer patients are at an increased risk of mortality. Within New York City, our community hospital emerged as an epicenter of the first wave of the pandemic in the spring of 2020 and serves a unique population that is predominately uninsured, of a lower income, and racially/ethnically diverse. In this single institution retrospective study, the authors seek to investigate COVID-19 diagnosis, severity and mortality in patients with an active cancer diagnosis. Demographic, clinical characteristics, treatment, SARS-CoV-2 laboratory results, and outcomes were evaluated. In our community hospital during the first wave of the COVID-19 pandemic in the United States, patients with active cancer diagnosis appear to be at increased risk for mortality (30%) and severe events (50%) due to the SARS-CoV-2 infection compared to the general population. A higher proportion of active cancer patients with Medicaid insurance, Hispanic ethnicity, other race, and male sex had complications and death from COVID-19 infection. The pandemic has highlighted the health inequities that exist in vulnerable patient populations and underserved communities such as ours.

Comparison of Pathologic Complete Response Rates and Oncologic Outcomes in Patients With Surgically Resectable Esophageal Cancer Treated With Neoadjuvant Chemoradiation to 50.4 Gy vs 41.4 Gy.

Background Excellent outcomes and high rates of pathologic complete response (pCR) have been reported in patients with operable esophageal carcinoma using 41.4 Gy of radiation with concurrent carboplatin and paclitaxel. With pCR rates similar to studies using higher doses, it remains unclear whether doses greater than 41.4 Gy result in improved outcomes. This study aims to compare pCR rates and oncologic outcomes in patients treated with neoadjuvant chemoradiation to 50.4 Gy vs 41.4 Gy. Methods We reviewed the charts of patients with operable esophageal carcinoma who were treated with neoadjuvant chemoradiation followed by oncologic resection. Our primary endpoint was the pCR rate. Secondary endpoints were overall survival, progression-free survival (PFS), and toxicity.  Results We identified 43 patients meeting inclusion criteria. Nineteen patients were treated with 41.4 Gy and 24 were treated with 50.4 Gy. Cohorts were well-matched, except for a significantly higher percentage of patients with adenocarcinoma (AC) (89.5% vs 54.2%, p = 0.02), usage of intensity-modulated radiation therapy (IMRT) (100% vs 47.6%; p = 0.002), and usage of carboplatin, plus paclitaxel (100% vs 75%; p = 0.003) in the 41.4 Gy group. The pCR rate for the cohort was 44.2%. No differences in the pCR rate (41.7% vs 47.4%), three-year overall survival (OS) (73.7% vs 77.5%), or three-year PFS (52.8% vs 43.7%) were observed. Late toxicity rates also did not vary significantly (p = 0.2). No grade 4 or 5 events were observed. Conclusion In this small series, there were no differences in the pCR rate, PFS, or OS between those treated with 50.4 Gy and 41.4 Gy. Larger, multi-institutional series are needed to validate these findings.

Risk of prolonged opioid use among cancer patients undergoing curative intent radiation therapy for head and neck malignancies.

OBJECTIVE: Patients undergoing radiation treatment (RT) for head and neck malignancies often suffer significant disease- and treatment-related pain requiring opioids for effective management. However, the prevalence and associated risk factors of prolonged opioid use in this population remain poorly characterized. We sought to quantify the rate of prolonged opioid use among opioid naïve patients receiving curative-intent RT for head and neck malignancies and to identify associated risk factors. METHODS: We retrospectively identified patients who had undergone RT for head and neck malignancies at our institution between Jan 2011 and Sept 2017. Our primary endpoint was persistent opioid use 6-months following completion of RT. Patients were included if they were opioid-naïve, underwent curative intent RT, had adequate follow-up, and did not have residual or recurrent disease within our follow-up period. Univariable and multivariable logistic regression was utilized to identify risk factors for prolonged opioid use. RESULTS: We identified 311 patients meeting our inclusion criteria; 40 (12.9%) continued to use opioids 6-months following RT. Univariable analysis found current smoking, alcohol abuse, RT dose, treatment to the bilateral necks, induction chemotherapy, concurrent chemotherapy, PEG tube, daily milligram morphine equivalents, and adjuvant analgesic medication use to be positively associated with prolonged opioid use; prior surgery was negatively associated with prolonged opioid use. Delivery of induction chemotherapy (OR 2.86, CI (95%) 1.32-6.21) and alcohol abuse (OR 3.75, CI (95%) 1.66-8.47) remained statistically significant on multivariable analysis. CONCLUSION: The prevalence of prolonged opioid use in previously opioid naïve patients undergoing curative intent head and neck RT was just under 13%. Patients with history of alcohol abuse and those who undergo induction chemotherapy were most at risk.

Utilization Patterns of Single Fraction Radiation Therapy for Multiple Myeloma.

BACKGROUND: Patients with multiple myeloma (MM) are living longer than ever before thanks to new therapies. As a consequence, radiation therapy (RT) is increasingly important in the management of bone lesions from MM. Current American Society for Radiation Oncology guidelines recommend greater usage of 8 Gy in 1 fraction for treatment of these lesions. The objective of this study is to analyze utilization of 8 Gy in 1 fraction for treatment of MM bone lesions in the United States utilizing the National Cancer Data Base (NCDB). MATERIALS AND METHODS: The NCDB was used to identify patients with MM treated with palliative RT for painful bony lesions in the period between 2004 and 2014. Utilization rate of RT in this patient population as well as single-fraction (SFRT) versus multiple-fraction RT (MFRT) was compared according to demographic, socioeconomic, and logistic details. RESULTS: A total of 95,190 patients met our inclusion criteria. Of these, 10,261 (10.8%) patients received RT, and a total of 243 (2.4%) of these patients received SFRT over the 10-year period. There was an 11.73% annual increase (P = .0001) in SFRT utilization from 2004 to 2014. Older age, black race, longer distance from the treatment facility, lower degree of education, treatment at an academic or integrated healthcare network, worse comorbidities, and more recent diagnoses were all associated with increased usage of SFRT. CONCLUSION: SFRT for the management of MM painful bony metastases remains underutilized. Trends show that radiation oncologists do not appear to be changing their approach to treating this disease.

The Safety Profile of Concurrent Therapy for Multiple Myeloma in the Modern Era.

PURPOSE: The management of multiple myeloma has evolved in the modern era, partially owing to the increasing number of biologic therapeutics. Nonetheless, radiation remains an important treatment in the management of painful lytic lesions from multiple myeloma. The goal of this study is to evaluate the side effect profile of radiation therapy (RT) while patients are concurrently treated with biologic agents. METHODS AND MATERIALS: We conducted a retrospective study based on data collected from patients receiving RT at our institute from 2007 to 2017. A total of 130 patients (279 treatment sites) were included in this study with a median follow-up time of 14 months. Patients were required to be receiving a biological agent at least within 1 month before starting and up to 1 month after RT. Generalized estimating equations with a log link function and binomial distribution were used to estimate the prevalence ratio (PR) and corresponding 95% confidence interval (CI) and compare the side effects between patients with RT alone and RT + biologic agent. RESULTS: The median age of all patients in our cohort was 64 years, with 53 men (58.9%) and 37 women (41.1%). The mean Karnofsky performance status score of all cohorts was 80. No significant difference in incidence of acute (PR: 1.33; 95% CI, 0.80-2.22; P = .2660) or subacute (PR: 0.90; 95% CI, 0.49-1.67; P = .7464) toxicities was found between patients with or without biologic agents who were treated concurrently with RT. No significant difference was found in reduction in laboratory values between patients with or without biologic agents treated concurrently with RT for white blood cells (P = .6916), platelets (P = .7779), or hematocrit (P = .0858). CONCLUSIONS: Our study did not detect any significant toxicity rates from palliative radiation while patients were concurrently treated with biologic agents.

Prostate-specific antigen doubling time is a significant predictor of overall and disease-free survival in patients with prostate adenocarcinoma treated with brachytherapy.

PURPOSE: Recently, new approaches have been implemented in treating patients with newly diagnosed metastatic prostate cancer (PCa). An interesting area of study is to determine which risk factors may be used as predictors of more aggressive PCa behavior in patients with biochemical failure. The aim of this study was to determine prognostic factors in patients with prostate-specific antigen (PSA) failure after undergoing brachytherapy. METHODS AND MATERIALS: Between 1990 and 2015, 2771 patients with localized PCa underwent treatment at our institution treated by a single radiation oncologist with low-dose-rate brachytherapy as a component of definitive radiation therapy. Disease-specific survival (DSS), distant metastases (DM), and overall survival were calculated by the Kaplan-Meier method. Multivariable Cox regression analysis was also performed. RESULTS: In this group, 2126 patients (89%) had no evidence of PSA failure. Of the 251 of patients that did have biochemical failure, 115 (45.8%), 58 (23.1%), 78 (31.1%) had a PSA doubling time (PSADT) of <6 months, 6-12 months, and >12 months, respectively. Doubling time was associated with a statistically significant impact on DSS and DM but not overall survival, which appears to be dominated by initial age at diagnosis as well as stage. CONCLUSIONS: We have shown here that PSADT predicts for DSS and freedom from DM in our large prospectively followed cohort. Given the variable trajectory of metastatic and recurrent PCa, strong prognostic factors such as PSADT may be able to select a group of patients who benefit from earlier or escalated systemic therapies such as androgen deprivation or cytotoxic chemotherapy.

Predictors of Complete Response and Disease Recurrence Following Chemoradiation for Rectal Cancer.

OBJECTIVE: Approximately 10-40% of rectal patients have a complete response (CR) to neoadjuvant chemoradiation (CRT), and these patients have improved survival. Thus, non-operative management ("watch-and-wait" approach) may be an option for select patients. We aimed to identify clinical predictors of CR following CRT. METHODS: Patients treated with definitive CRT for T3-T4, locally unresectable T1-T2, low-lying T2, and/or node-positive rectal cancer from August 2004 to February 2015 were retrospectively reviewed. Most patients were treated with 50.4 Gy radiation and concurrent 5-fluoruracil or capecitabine. Patients were considered to have a CR if surgical pathology revealed ypT0N0M0 (operative management), or if they had no evidence of residual disease on clinical and radiographic assessment (non-operative management). Statistical analysis was carried out to determine predictors of CR and long-term outcomes. RESULTS: Complete records were available on 138 patients. The median follow-up was 24.5 months. Thirty-six patients (26.3%) achieved a CR; 30/123 operatively managed patients (24.5%) and 6/15 (40%) non-operatively managed patients. None of the 10 patients with mucinous adenocarcinoma achieved a CR. Carcinoembryonic antigen (CEA) ≥5 µg/L at diagnosis (OR 0.190, 95% CI 0.037-0.971, p = 0.046), tumor size ≥3 cm (OR 0.123, 95% CI 0.020-0.745, p = 0.023), distance of tumor from the anal verge ≥3 cm (OR 0.091, 95% CI 0.013-0.613, p = 0.014), clinically node-positive disease at diagnosis (OR 0.201, 95% CI 0.045-0.895, p = 0.035), and interval from CRT to surgery ≥8 weeks (OR 5.267, 95% CI 1.068-25.961, p = 0.041) were independent predictors of CR. The CR group had longer 3-year distant metastasis-free survival (DMFS) (93.7 vs. 63.7%, p = 0.016) and 3-year disease-free survival (DFS) (91.1 vs. 67.8%, p = 0.038). Three-year locoregional control (LRC) (96.6 vs. 81.3%, p = 0.103) and overall survival (97.2 vs. 87.5%, p = 0.125) were higher in the CR group but this did not achieve statistical significance. CR was not an independent predictor of LRC, DMFS, or DFS. CONCLUSION: CEA at diagnosis, tumor size, tumor distance from the anal verge, node positivity at diagnosis, and interval from CRT to surgery were predictors of CR. These clinical variables may offer insight into patient selection and timing of treatment response evaluation in the watch-and-wait approach.

Outcomes of rectal cancer with liver oligometastases.

PURPOSE: In patients with oligometastatic colorectal cancer to the liver, long term survival is possible and a multi-modality treatment approach may be considered. This is a report of a single institution experience of oligometastatic rectal cancer patients after treatment of the primary tumor and pelvic lymph nodes with extended course chemoradiation therapy. METHODS: Between 2004 and 2013, 26 oligometastatic rectal cancer patients with liver metastases were treated with extended course chemoradiation at our institution followed by total mesorectal excision (TME). Amongst these there were 17 men and 9 women. The mean age at the time of diagnosis was 59.8 years, with a range from 36 to 87 years of age. Eleven patients had metastases in other sites in addition to liver, and one patient in our cohort had lung metastasis with no liver metastasis. Kaplan-Meier method was used to generate overall survival (OS), progression free survival (PFS), distant metastases (DM) and local control (LC). RESULTS: OS rates were 95%, and 70% at 12 and 24 months respectively, with a mean survival time of 40.5 months. PFS rates were 91% and 36% at 12 and 24 months respectively, with a mean PFS time of 23.1 months. LC rates were 91% and 66% at 12 and 24 months respectively. DM rates were 0% and 61% at 12 and 24 months respectively. Finally, when censoring deaths, progression of liver metastases and distant progression, Kaplan-Meier analysis demonstrated five events of local failure. CONCLUSIONS: This series demonstrated an OS of 70% at 24 months, with a mean survival of 40.5 months. Significantly, LC was only 66% despite the use of extended course chemoradiation and TME. This data suggests that many patients with oligometastatic rectal cancer will survive past 2 years, and that a substantial number will fail locally as well as distantly. Therefore, a multimodality approach is reasonable. Recent data suggests that a hypofractionated radiation regiment of 25 Gy in 5 Gy fractions allows an equivalent LC compared to extended course chemoradiation with 50.4 Gy in 1.8 Gy fractions. A short course of radiation may be more consistent with the goals of care of the oligometastatic rectal cancer patient who is at high risk of recurrence.