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.

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.

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.

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.

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.

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.

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.

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.

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.