Long-term clinical outcomes of [177Lu]Lu-DOTATATE in patients with metastatic neuroendocrine tumors.

The incidence of gastroenteropancreatic neuroendocrine tumors has been rising and these tumors are usually only diagnosed at a metastatic stage. Present first line treatments include somatostatin analogs, targeted therapies and peptide receptor radionuclide therapy. The Lutetium-177 [177Lu] based radiotracer [177Lu]Lu-DOTATATE has only been approved as first-line treatment of metastatic midgut NETs however its efficacy as a third line or above treatment in patients with non ileal primaries has not been tested. In our study, we identified 25 patients with histologically confirmed well-differentiated metastatic neuroendocrine tumors and administered [177Lu]Lu-DOTATATE as a second line, third line and fourth line treatment. Our study demonstrated a notable response in patients with non-ileal primaries and heavily pretreated disease, warranting further studies for additional cycles of treatment.

Bevacizumab-Induced Cutaneous Lupus Erythematosus in a Patient With Metastatic Colon Carcinoma: A Case Report.

Bevacizumab, an anti-vascular epidermal growth factor inhibitor, is approved for the treatment of various cancers. Hypertension, gastrointestinal perforation, bleeding manifestations, impaired wound healing, and cerebrovascular accidents are common side effects associated with the monoclonal antibody. Uncommon cutaneous reactions like exfoliative dermatitis associated with bevacizumab have been documented in the medical literature. We present an unusual case of bevacizumab-induced cutaneous lupus in a patient with metastatic colon cancer that started resolving after discontinuing chemotherapy. Timely intervention was key in preventing the progression of this chemotherapy-induced cutaneous lupus.

Nutritional Composition, Mineral Profiling, In Vitro Antioxidant, Antibacterial and Enzyme Inhibitory Properties of Selected Indian Guava Cultivars Leaf Extract.

Psidium guajava L. is a small evergreen tree known for its magnificent medicinal and nutritional value. This study aimed to evaluate the nutritional profile and in vitro pharmacological potentialities of the different leaf extracts of four cultivars of Psidium guajava namely Surka chitti, Allahabad safeda, Karela, and Lucknow-49. The standard procedures of the Association of Official Analytical Chemists (AOAC) were followed to carry out the nutritional analysis and all of the cultivars recorded the presence of elements at a nominal range. The highest presence of phenols (125.77 mg GAE/g) and flavonoids (92.38 mg QE/g) in the methanolic leaf extract of the Karela cultivar was recorded. A wide range of minerals such as sodium, phosphorus, magnesium, zinc, and boron were recorded with a higher percentage in the Karela cultivar of Psidium guajava. In the enzyme inhibitory assays, Allahabad safeda showed potential inhibition with an IC50 of 113.31 ± 1.07, 98.2 ± 0.66 and 95.73 ± 0.39 µg/mL in α-amylase, α-glucosidase, and tyrosinase inhibition assays, respectively. The strong antioxidant effect was established by Lucknow-49 (IC50 of 74.43 ± 1.86 µg/mL) and Allahabad safeda (IC50 of 78.93 ± 0.46 µg/mL) for ABTS and DPPH assays, respectively. The ethyl acetate and methanolic leaf extracts of the Allahabad safeda cultivar showed better inhibition against Pseudomonas aeruginosa with an MIC of 14.84 and 28.69 µg/mL, respectively. A decent mean zone of inhibition was recorded in methanolic leaf extract that ranged from 21-25 mm in diameter against the tested bacterial strains (Proteus vulgaris, Bacillus subtilis, and P. aeruginosa). This is the first scientific report on the comparative and comprehensive analysis of indigenous guava cultivars to evidently shortlist the elite cultivars with enriched dietary nutrition and biological activities.

The Influence of the Microbiome on Immunotherapy for Gastroesophageal Cancer.

Immunotherapy has shown promise as a treatment option for gastroesophageal cancer, but its effectiveness is limited in many patients due to the immunosuppressive tumor microenvironment (TME) commonly found in gastrointestinal tumors. This paper explores the impact of the microbiome on the TME and immunotherapy outcomes in gastroesophageal cancer. The microbiome, comprising microorganisms within the gastrointestinal tract, as well as within malignant tissue, plays a crucial role in modulating immune responses and tumor development. Dysbiosis and reduced microbial diversity are associated with poor response rates and treatment resistance, while specific microbial profiles correlate with improved outcomes. Understanding the complex interactions between the microbiome, tumor biology, and immunotherapy is crucial for developing targeted interventions. Microbiome-based biomarkers may enable personalized treatment approaches and prediction of patient response. Interventions targeting the microbiome, such as microbiota-based therapeutics and dietary modifications, offer the potential for reshaping the gut microbiota and creating a favorable TME that enhances immunotherapy efficacy. Further research is needed to reveal the underlying mechanisms, and large-scale clinical trials will be required to validate the efficacy of microbiome-targeted interventions.

Alectinib-induced rash unresponsive to desensitization: a case report and literature review.

BACKGROUND: Since the inception of targeted therapies in treating lung cancer, providers have had to be aware of a new host of side effects when selecting management options for patients. Although targeted therapies are creating increased hope for patients with non-small cell lung cancers (NSCLC), understanding their side effects presents a challenge for providers. Alectinib, a second-generation tyrosine kinase inhibitor, is a targeted therapy used in patients with non-small cell lung cancer found to have anaplastic lymphoma kinase (ALK) mutations. Alectinib is the focus of this case report and literature review as we seek to understand side effects providers may encounter when prescribing these therapies. CASE PRESENTATION: We begin our report with the case of a 63-year-old Hispanic female with stage IIIA non-small cell lung cancer found to have the ALK genomic alteration. She was started on Alectinib, and on Day 11, she developed a severe maculopapular rash requiring hospitalization. After complete resolution, desensitization with Alectinib was attempted but unsuccessful. CONCLUSIONS: Despite the unsuccessful desensitization of this patient, it is important to report this rare side effect in order to better understand how providers can pursue management. Case reports such as this can aid providers in potentially preventing, treating, and rechallenging patients on targeted therapies in the future.

Paraneoplastic Necrotizing Myopathy Associated With Metastatic Colon Cancer: A Case Report.

Necrotizing myopathy (NM) as a paraneoplastic process in malignancies is a rare phenomenon. An association of inflammatory myositis with malignancy and chemotherapies has been reported in several case reports. Here, we present an unusual case of paraneoplastic NM associated with metastatic colon cancer.

Anaplastic Lymphoma Kinase (ALK) Mutation-Targeting Treatment With Alectinib in Lung Adenocarcinoma and Primary Cutaneous Marginal Zone B-Cell Lymphoma.

Lung adenocarcinoma or non-small cell lung cancer (NSCLC) represents one of the most diagnosed cancers worldwide. Anaplastic lymphoma kinase (ALK) mutation, a tyrosine kinase and ALK fusion or rearrangement oncogene, has been found rarely in patients with NSCLC. Newer treatment modalities with different ALK inhibitors in targetable specific ALK mutations have recently made great strides in the management of NSCLC patients. We present a case of NSCLC harboring ALK mutation with primary cutaneous marginal zone B-cell lymphoma (PCMZL) treated with adjuvant chemotherapy with pemetrexed and cisplatin, and ALK-echinoderm microtubule-associated protein-like 4 (EML4)-targeting treatment alectinib.

Rechallenging Fluoropyrimidine-Induced Cardiotoxicity and Neurotoxicity: A Report of Two Cases.

Fluoropyrimidines (FP's) such as fluorouracil (5-FU) and capecitabine are antimetabolites widely used in many solid tumors. FPs side effects are caused mainly by a lack of dihydropyrimidine dehydrogenase (DPD) enzyme. It has been noticed that treatment with infusional regimens of 5-FU is associated with more adverse events (AE) compared to bolus forms. Here, we report two cases of unusual side effects seen with infusional 5-FU and capecitabine and how early intervention by withholding ongoing treatment can help in preventing progression and mortality.

Importance of Early Next-Generation Sequencing in Microsatellite Unstable Colon Cancer With a High Tumor Mutation Burden.

Colon cancer is one of the leading causes of cancer-related deaths. Microsatellite instability (MSI) or deficient mismatch repair proteins with a high tumor mutation burden (TMB) colon cancer are less responsive to chemotherapy. Targeted therapies based on early next-generation sequencing (NGS) in metastatic colon cancer can help significantly in overall prognosis. Here, we report a case of colon cancer that illustrated significant TMB and MSI and responded poorly to treatment due to delay in NGS testing.

Analysis of Post-operative Adjuvant Chemotherapy Versus Adjuvant Chemoradiation Therapy Outcomes in Non-metastatic Cholangiocarcinoma: an NCDB Review.

BACKGROUND: Each year, approximately 8000 cases of cholangiocarcinoma are recorded in the USA. Surgical resection is considered to be the only curative option. Despite surgery as a curative approach, many patients will require adjuvant therapies in the form of chemotherapy (ChT) or chemoradiotherapy (CRT). As such, we sought to analyze outcomes in patients with non-metastatic cholangiocarcinoma receiving adjuvant ChT or CRT following surgical resection. METHODS: We queried the National Cancer Database (NCDB) for patients with a diagnosis of non-metastatic cholangiocarcinoma between the years 2010 and 2015 who underwent adjuvant ChT or CRT following surgery. Overall survival (OS) was calculated using Kaplan Meier method. Cox proportional hazard ratios were used to identify predictors of overall survival, and logistic regression was used to identify predictors of receiving each treatment. RESULTS: A total of 875 patients were identified who met the above eligibility criteria. Of these patients, 818 received adjuvant chemotherapy alone with 57 patients receiving adjuvant chemoradiation therapy. The median OS in patients receiving CRT was 19.8 months versus 11.9 months for ChT (p value < 0.0238). The 1- and 5-year survival rates between ChT and CRT were 50% vs 61% and 6% vs 13%, respectively (hazard ratio 0.7005; 95% CI 0.51-0.97; p value < 0.0294). CONCLUSION: The results of this study suggest a potential benefit of chemoradiation therapy in the adjuvant setting, although the trends appear to show rare utilization. Given the limitations of our study, prospective corroboration is warranted.

Pembrolizumab-Induced Lichenoid Dermatitis in a Patient With Metastatic Cancer of Unknown Primary.

Pembrolizumab is an immune checkpoint inhibitor approved for use in many cancer types such as non-small cell lung cancer (NSCLC), metastatic melanoma, head and neck cancers, hepatocellular carcinoma, and renal cell carcinoma. There are many reported cases of patients on immunotherapy who have discontinued treatment due to the development of immune-related adverse effects (irAE). Recognition of the histopathologic patterns of dermatologic toxicities due to immunotherapy will become increasingly important for ensuring appropriate management and optimal patient care. Here, we present a case of a 72-year-old man with metastatic carcinoma of unknown primary origin treated with pembrolizumab who developed an immune-related cutaneous adverse event (ircAE) in the form of lichenoid dermatitis.

A Retrospective Analysis of Factors Affecting Palliative Care Consults in Patients Undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

Purpose This study was conducted to determine factors that influence palliative care (PC) consultation in patients receiving cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Patient and methods We queried our Electronic Medical Record EPIC for a list of patients who underwent cytoreductive surgery with HIPEC or hyperthermic intrathoracic chemotherapy (HITEC) in the hospital from April 2016-April 2019. Data was manually extracted and patients who did not meet our criteria were excluded. Patients were divided on the basis of palliative care consults and differences between the groups were analyzed. Odds ratios (OR) with p-value of 0.05 and confidence interval of (CI) 95% were calculated. Results We identified 55 patients of whom 34 met our inclusion criteria: 11 males and 23 females with an average age of 56 years at the time of diagnosis. Eight patients (23%) had PC, with six having commercial insurance, seven married, and six with more than one comorbid medical issue. Comorbidities >1 (OR: 0.12; CI: 0.02-0.76; p: 0.02) and age >40 (OR: 0.015; CI: 0.0007-0.3029; P: 0.006) were associated with a higher likelihood of PC. Gender, insurance type, and marital status did not have a significant association with PC. Mean age between PC consulted patients versus non-PC consulted patients was 58.5 vs. 55.9 and median age between the two groups was 60.5 vs. 60 which also showed a trend towards higher rates of PC in the older population. Conclusion Approximately one quarter of patients who underwent CRS with HIPEC had a concurrent PC consult. Though this is better than the national average of 11-16%, it continues to be a very small number. Efforts must be made to engage PC early in the course of treatment and recognize it as an integral part of cancer care. PC is not only an end-of-life service, in fact, studies have shown that early consultations lead to higher patient satisfaction, improved quality of life, and better communication.

Atypical Mycobacterium Abscessus Infection in Stable Chronic Lymphocytic Leukemia: A Case Report and Review of the Literature.

Chronic lymphocytic leukemia is the most common blood cancer in adults. A major cause of morbidity and mortality associated with this cancer stems from opportunistic infections. Similar to many cancers, the inherent effects of battling a raging disease along with the many treatment options causing immunosuppression to lend to the likelihood of obtaining secondary infections. As it is important for physicians to note the ever-increasing secondary complications, which can manifest in the long-term management of immunosuppressed patients, we present a case of an 86-year-old Caucasian female with stable chronic lymphocytic leukemia who developed intermittent presentation of lung abscesses due to growth of atypical Mycobacterium species. With the advent of new treatment options, there has been an increased rate of drug-resistant organisms, lending for the need for more awareness to the severity of these secondary complications and for better options in preventing their occurrence.

Microsatellite Instability (MSI) as an Independent Predictor of Pathologic Complete Response (PCR) in Locally Advanced Rectal Cancer: A National Cancer Database (NCDB) Analysis.

OBJECTIVE: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. BACKGROUND: We utilized the National Cancer Database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. METHODS: We analyzed 5086 patients between 2010 and 2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional-hazard ratios were used for survival. RESULTS: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher-grade tumors (P < 0.05).The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (odds ratio 0.65, 95% confidence interval 0.43-0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared with 73% without it (<0.001). CONCLUSION: Microsatellite instability was independently associated with a reduction in pCR for locally advanced rectal cancer after neoadjuvant chemoradiation in this NCDB-based analysis.

Utilization of Adjuvant Radiotherapy for Resected Colon Cancer and Its Effect on Outcome.

BACKGROUND: Adjuvant radiation is generally not recommended for colon cancer but may be considered in certain clinical scenarios [advanced local disease (pT4) and/or positive margins]. Guidelines in this area are lacking; thus we analyzed the National Cancer Database (NCDB) for patterns of care in this regard and any predictors for outcome. METHODS: We queried the NCDB from 2004 to 2016 for patients with resected adenocarcinoma of the colon having pT4 and/or had positive margins on final pathology and who received adjuvant multiagent chemotherapy. Multivariable logistic regression was used to identify predictors of adjuvant radiation. A propensity score was used to perform matched Kaplan-Meier analysis. Propensity-adjusted Cox regression was used to identify predictors of overall survival. RESULTS: We identified 23,325 patients meeting criteria, of whom 1711 (7%) received adjuvant radiation. Median follow-up was 36 months. The majority of patients were pT4 alone (65%). Predictors of adjuvant radiation were lower comorbidity score, younger age, more remote year of treatment, and both pT4 and positive margins. Kaplan-Meier analysis revealed improved overall survival (OS) in patients with both pT4 and positive margins treated with radiation (median OS: 66 versus 47 months, p = 0.02). Receipt of adjuvant radiation was associated with improved OS [hazard ratio (HR): 0.86 (0.80-0.93) p = 0.0002] on Cox regression analysis. Increased age, higher comorbidity score, lower income, government insurance, and combined pT4/positive margins were indicative of worse survival. CONCLUSIONS: Expectedly, adjuvant radiation use was relatively low but was associated with improved OS in patients with both pT4 and positive margins.

Retrospective review of total neoadjuvant therapy.

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by resection and postoperative multi-agent chemotherapy (maChT) is the standard of care for locally advanced rectal cancer. Using this approach, maChT administration can be delayed for several months, leading to concern for distant metastases. To counteract this, a novel treatment approach known as total neoadjuvant therapy (TNT) has gained popularity, in which patients receive both maChT and nCRT prior to resection. We utilized the National Cancer Database to examine temporal trends in TNT usage, and any potential effect on survival. AIM: To study the temporal trends in the usage of TNT and evaluate its efficacy compared to neoadjuvant chemoradiation. METHODS: We queried the National Cancer Database for patients with locally advanced rectal cancer, Stage II-III, from 2004-2015 treated with nCRT or TNT. TNT was defined as maChT initiated ≥ 90 d prior to nCRT initiation. Overall survival was calculated from the date of diagnosis to the date of last contact or death using Kaplan-Meier curves to present the cumulative probability of survival, with log-rank statistics to assess significance. Multivariable cox regression was used to identify predictors of survival and propensity score analysis accounted for bias. RESULTS: We identified 9066 eligible patients, with 8812 and 254 patients receiving neoadjuvant chemoradiation followed by maChT and TNT, respectively. Nodal involvement, stage III disease, and treatment in recent years were predictive of TNT use. There was greater use of TNT with more advanced stage, specifically > 1 node involved (odds ratio [OR] = 2.88, 95% confidence interval [CI]: 2.11-3.93, P < 0.01) and stage III disease (OR = 2.88, 95%CI: 2.11-3.93, P < 0.01). From 2010 to 2012 the use of TNT increased (OR = 2.41, 95%CI: 1.27-4.56, P < 0.01) with a greater increase from 2013 to 2015 (OR = 6.62, 95%CI: 3.57-12.25, P < 0.01). Both the TNT and neoadjuvant chemoradiation arms had a similar 5-year survival at 76% and 78% respectively. Multivariable analysis with propensity score demonstrated that increased age, high comorbidity score, higher grade, African American race, and female gender had worse overall survival. CONCLUSION: Our data demonstrates a rising trend in TNT use, particularly in patients with worse disease. Patients treated with TNT and nCRT had similar survival. Randomized trials evaluating TNT are underway.

Definitive Chemoradiation for Rectal Cancer: Is There a Role for Dose Escalation? A National Cancer Database Study.

BACKGROUND: Surgery remains the standard of care in rectal cancer. Select patients will not undergo surgery for reasons such as medical inoperability or a watch-and-wait approach and instead are managed with definitive chemoradiation. OBJECTIVE: We used the National Cancer Database to identify overall survival and predictors thereof in the nonoperative management of patients with rectal cancer. DESIGN: This was a retrospective review. SETTINGS: This study used deidentified data from the National Cancer Database. PATIENTS: We queried the national cancer database from 2004 to 2014 for stage 1 to 3 rectal adenocarcinoma treated with only chemotherapy and radiation to definitive doses. Dose escalated therapy was defined as >54 Gy. MAIN OUTCOME MEASURES: Univariable and multivariable analyses were performed to identify sociodemographic, treatment, and tumor characteristics predictive of dose escalation and overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: Among the 6311 patients eligible for the study, 11% were treated with doses >54 Gy. Earlier stage and increased age/comorbidity patients were more likely to receive dose escalation, and patients with more recent treatment and treatment at an academic facility were less likely. The median follow-up time was 31 months (range, 2-154 mo). Three- and 5-year overall survival rates for all patients were 60% and 46%. Patients treated with dose escalation had a median survival of 33 months compared with 56 months for those treated with ≤54 Gy (p < 0.0001). LIMITATIONS: The main limitation is the inherent selection bias present in National Cancer Database studies. Important treatment details and outcomes as they relate to a definitive chemoradiation approach in rectal cancer are lacking. Salvage therapy was also not recorded, which in this population could be surgery. CONCLUSIONS: In this analysis, dose escalation in the nonoperative management of rectal cancer was associated with a lower overall survival compared with more conventional doses. Careful patient selection and enrollment on appropriate clinical trials may be warranted in the nonoperative setting. See Video Abstract at http://links.lww.com/DCR/B15. LA QUIMIORRADIACIÓN DEFINITIVA PARA EL CÁNCER RECTAL: ¿HAY LUGAR PARA EL AUMENTO DE LA DOSIS? UN ESTUDIO DE BASE DE DATOS NACIONAL DEL CÁNCER:: La cirugía sigue siendo el estándar en el tratamiento del cáncer rectal. Algunos pacientes no son quirúrgicos por razones como, no ser operables o con el enfoque de ver y esperar, y en su lugar son tratados con la quimiorradiación definitiva.Utilizamos la base de datos nacional del cáncer para identificar la supervivencia general y los factores predictivos de la misma, en el tratamiento no quirúrgico de pacientes con cáncer rectal.Esta fue una revisión retrospectiva.Utilizamos los datos identificados en la base de datos nacional del cáncer.Se consultó la base de datos nacional del cáncer del 2004-2014, para adenocarcinoma rectal en estadio 1-3, tratada únicamente con quimioterapia y radiación hasta la dosis definitiva. La terapia de aumento de la dosis se definió como >54 Gy.Se realizaron análisis univariables y multivariables para identificar características sociodemográficas, de tratamiento y predictivas del aumento de la dosis y supervivencia en general. Los índices de riesgo proporcionales de Cox ajustados a la propensión para la supervivencia, se utilizaron para tener en cuenta el sesgo de indicación.Entre los 6311 pacientes elegibles para el estudio, el 11% fue tratado con dosis >54 Gy. Los pacientes en estadios tempranos y con mayor edad/comorbilidad, tenían más probabilidades de recibir aumento de la dosis, y menos propensos los pacientes con tratamientos recientes y de centros académicos. El tiempo medio de seguimiento fue de 31 meses (2-154 meses). Las tasas de supervivencia global de tres y cinco años para todos los pacientes, fueron respectivamente del 60% y 46%. Los pacientes tratados con aumento de la dosis, tuvieron una supervivencia media de 33 meses, en comparación con los 56 meses para los pacientes tratados con ≤54 Gy (p < 0,0001).La principal limitación es el inherente sesgo en la selección, presente en los estudios de la base de datos nacional del cáncer. Faltan los detalles importantes del tratamiento y los resultados en relación con el enfoque definitivo de quimiorradiación en cáncer rectal. Tampoco se registró la terapia de rescate, que en esta población podría ser la cirugía.En este análisis, el aumento de la dosis en el manejo no quirúrgico del cáncer rectal, se asoció con una menor supervivencia global, en comparación con la dosis más convencional. La cuidadosa selección del paciente y la inscripción en los apropiados ensayos clínicos, pueden estar justificados en el entorno no quirúrgico. Vea el Resumen del Video en http://links.lww.com/DCR/B15.

Anal adenocarcinoma: Treatment outcomes and trends in a rare disease entity.

IMPORTANCE: Primary Adenocarcinoma of the anus is a rare disease with a poor prognosis and thus tends to have a more aggressive treatment algorithm, typically involving a surgical approach. Prior to 2001, a few retrospective studies outlined improved outcomes with the incorporation of surgery with chemoradiation. However, since the publication of these studies, advancement in radiotherapy modalities and imaging have left the question of improved outcomes while reserving surgery for salvage. OBJECTIVE: We conducted this National Cancer Database (NCDB)-driven retrospective study to analyze treatment trends and outcomes in the current time from 2004 to 2015 with respect to chemoradiation and surgery. DESIGN: Retrospective NCDB tumor registry data review-using propensity score-adjusted multivariable analyses for survival. SETTING: Database review. PARTICIPANTS: We selected for patients listed in the NCDB with AJCC stage 1-3 anal adenocarcinoma diagnosed between 2004 and 2015 and selected out patients with undocumented/stage 4 disease, those with radiation outside the pelvis, not treated with systemic therapy and patients lost to follow-up. EXPOSURE(S): None. MAIN OUTCOMES AND MEASURES: Overall survival and use of surgery in the up-front management of anal adenocarcinoma. RESULTS: Of the 1729 patients eligible in this study, 1028 were treated with surgery as up-front management and 701 had definitive chemoradiation. Median overall survival for all patients was 55 months with a 5-year survival rate of 55%. Patients treated without surgery had worse overall survival, median survival of 45 months compared to 87 months (P < 0.0001) with 5-year survival rates of 42% and 55% in favor of incorporation of surgery. Analysis across patients treated with surgery alone, surgery followed by adjuvant chemoradiation, neoadjuvant chemoradiation followed by surgery, and chemoradiation alone had median survival rates of 78, 83, 92, and 46 months, respectively. Propensity score-adjusted multivariable analysis identified older age, grade 3, high comorbidity score, and lack of surgery as predictive of worse outcome. CONCLUSIONS AND RELEVANCE: The results of the NCDB analysis indicate improved overall survival with the incorporation of surgery into the initial management of anal adenocarcinoma when compared to chemoradiation alone, despite the omission of surgery in up to 50% of the cases logged. Our results corroborate earlier studies published prior to the year 2000 for surgery to be included in the definitive management of anal adenocarcinoma.

Trends in Radiation Dose and Technique For Anal Canal Squamous Cell Carcinoma.

BACKGROUND: Anal canal squamous cell carcinoma (SCC) is managed definitively with chemoradiation, reserving surgery for salvage. The dosage of radiation has varied from 30 Gy to in excess of 60 Gy. RTOG 0529 established intensity modulated radiation therapy (IMRT) as standard of care for anal canal SCC with doses of 50.4 to 54 Gy. We sought to use the National Cancer Database to examine trends in dose selection and radiation technique over time. METHODS: We queried the National Cancer Database from 2004 to 2015 for cases of anal cancer stage groups 1 to 3, treated with definitive doses of radiation with chemotherapy. Dose escalation was defined as >54 Gy. Univariable and multivariable analyses were performed to identify factors predictive of dose, IMRT, and overall survival. Propensity-adjusted Cox proportional hazard ratios for survival were used to account for indication bias. RESULTS: We identified 7792 patients meeting the eligibility criteria, with 4269 treated to doses of 45 to 54 Gy and 3163 treated to doses >54 Gy. Patients who were older, had government or private insurance, IMRT treatment, treatment at an academic center, or more recent years were less likely to get dose escalation. The use of dose escalation decreased over time, from 50% in 2005 to 30% in 2015. IMRT use increased over time from 2% to 63%. On multivariable analysis with propensity score included it was found that increased age, higher comorbidity score, lower income, shorter distance to facility, and male sex were predictive of decreased overall survival. In addition, escalated dose was associated with a lower survival (hazard ratio: 1.10, 95% confidence interval: 1.01-1.20, P=0.03). CONCLUSIONS: The results of this analysis show a steady increase in the use of IMRT, with corresponding decrease in dose escalation. These findings correlate with the results of RTOG 0529 establishing IMRT as standard of care for anal SCC, using doses of 50.4 to 54 Gy.

Chemotherapy Versus Supportive Care for Unresected Malignant Pleural Mesothelioma.

BACKGROUND: Management options for unresected malignant pleural mesothelioma (MPM) are largely limited to palliative chemotherapy and best supportive care. This study sought to delineate subgroups most likely to benefit from chemotherapy. PATIENTS AND METHODS: The National Cancer Database was queried for newly-diagnosed unresected sarcomatoid, biphasic, and/or metastatic (M1) MPM. Statistics included Kaplan-Meier overall survival (OS) analysis with and without propensity matching, landmark Kaplan-Meier analysis to address immortal time bias, and multivariable Cox proportional hazards modeling in all patients as well as within histologic/M-classification-based subcohorts. RESULTS: Of 4655 patients (48% chemotherapy, 52% best supportive care), 15%, 27%, and 40% had epithelioid, biphasic, and sarcomatoid disease, respectively; 41% had M1 disease. The median OS in the chemotherapy and BSC cohorts was 10.4 versus 4.8 months (P < .001). OS differences persisted following landmark analysis (P = .038) and propensity matching (P < .001). Chemotherapy was associated with higher OS in M1 cases with unknown histology and M1 epithelioid patients (P < .001 for both). For non-epithelioid cases, chemotherapy was associated with higher OS for M0 (P < .001 for sarcomatoid and biphasic) but not M1 (P > .05 for both) disease. CONCLUSIONS: Chemotherapy may benefit metastatic epithelioid and non-metastatic non-epithelioid MPM to a greater degree than metastatic non-epithelioid disease. Causation, however, is not implied, and careful patient selection in this population cannot be understated.