Clinical Determinants Differentiating the Severity of SARS-CoV-2 Infection in Cancer Patients: Hospital Care or Home Recovery.

Background: Cancer patients may carry a worse prognosis with SARS-CoV-2 infection. Most of the previous studies described the outcomes of hospitalized cancer patients. We aimed to study the clinical factors differentiating patients requiring hospital care vs. home recovery, and the trajectory of their anti-cancer treatment. Methods: This study was conducted in a community cancer center in New York City. Eligible patients were those who had cancer history and were diagnosed of SARS-CoV-2 infection between March 1 and May 30, 2020, with confirmatory SARs-CoV-2 virus test or antibody test. Four groups were constructed: (A) hospitalized and survived, (B) hospitalized requiring intubation and/or deceased, (C) non-hospitalized, asymptomatic, with suspicious CT image findings, close exposure, or positive antibody test, and (D) non-hospitalized and symptomatic. Results: One hundred and six patients were included in the analysis. Thirty-five patients (33.0%) required hospitalization and 13 (12.3%) died. Thirty (28.3%) patients were asymptomatic and 41 (38.7%) were symptomatic and recovered at home. Comparing to patients who recovered at home, hospitalized patients were composed of older patients (median age 71 vs. 63 years old, p = 0.000299), more who received negative impact treatment (62.9 vs. 32.4%, p = 0.0036) that mostly represented myelosuppressive chemotherapy (45.7 vs. 23.9%, p = 0.0275), and more patients with poorer baseline performance status (PS ≥ 2 25.7 vs. 2.8%, p = 0.0007). Hypoxemia (35% in group A vs. 73.3% in group B, p = 0.0271) at presentation was significant to predict mortality in hospitalized patients. The median cumulative hospital stay for discharged patients was 16 days (range 5-60). The median duration of persistent positivity of SARS-CoV-2 RNA was 28 days (range 10-86). About 52.9% of patients who survived hospitalization and required anti-cancer treatment reinitiated therapy. Ninety-two percent of the asymptomatic patients and 51.7% of the symptomatic patients who recovered at home continued treatment on schedule and almost all reinitiated treatment after recovery. Conclusions: Cancer patients may have a more severe status of SARS-CoV-2 infection after receiving myelosuppressive chemotherapy. Avoidance should be considered in older patients with poor performance status. More than two thirds of patients exhibit minimal to moderate symptoms, and many of them can continue or restart their anti-cancer treatment upon recovery.

Stereotactic Ablative Radiotherapy Fractionation for Hepatocellular Carcinoma in the United States.

Introduction This study aims to analyze the patterns of care, including fractionation and utilization, of hypofractionated stereotactic ablative radiotherapy (SABR) in the treatment of hepatocellular carcinoma (HCC). Methods The National Cancer Database was queried for patients diagnosed with HCC from 2004 to 2014 and treated with SABR in three, four, or five fractions in 15-20Gy, 10-13Gy, or 6-12Gy per fraction, respectively. Patients with stage IV and Charlson-Deyo Comorbidity Index > 0 were excluded in order to avoid bias resulting from the selection of poorer prognosis patients. The patients were then stratified based on several characteristics including biologically equivalent doses (BEDs) of =/> 100 Gy and <100 Gy to determine whether there was an association with overall survival (OS) and a multivariable analysis (MVA) was performed to assess for potential confounding factors.  Results There were 462 patients identified in whom the most common SABR fractionation regimen was 10Gy x five fractions (25.3%), followed by 8Gy x five fractions (17.7%), and 15-16Gy x three fractions (26.4%). A total of 152 patients were treated to a BED < 100Gy, which was associated with a median OS of 20.8 months (95% CI 14.55-27.11). Three hundred and ten patients were treated to a BED =/> 100Gy, which was associated with a median OS of 30.8 months (95% CI 5.25-32.08). On MVA, BED =/> 100Gy was not significantly associated with improved OS (HR 0.85, 95% CI 0.64-1.14, p = 0.28). Factors that were associated with significantly worse survival were tumor size in the largest quartile (HR 2.197 CI 1.440-3.354, p < 0.0001) and T3a disease (HR 2.474 CI 1.472-4.158, p = 0.001 compared to T1).  Conclusion SABR fractionation schemes vary widely, but are most commonly 10Gy x five fractions followed by 8Gy x five fractions and 15Gy x three fractions. BED of at least 100Gy is not associated with improved OS. Further studies are needed to best identify the optimal SABR dose and fractionation.

Patterns of Care and Comparison of Outcomes Between Primary Anal Squamous Cell Carcinoma and Anal Adenocarcinoma.

BACKGROUND: The management of adenocarcinoma of the anus can be challenging because there are few data on outcomes and trends in its treatment to date. OBJECTIVE: This study aimed to compare and analyze the patterns of care and survival outcomes of patients with anal squamous cell carcinoma and anal adenocarcinoma. DESIGN: This was a retrospective study. SETTING: This study was performed by utilizing the National Cancer Database. PATIENTS: We selected a total of 19,539 patients between 2004 and 2014 with stage II to III squamous cell carcinoma or adenocarcinoma of the anus. INTERVENTION: The treatment groups analyzed were surgery alone, neoadjuvant chemoradiation followed by surgery, surgery followed by adjuvant chemoradiation, or definitive chemoradiation. MAIN OUTCOME MEASURES: Patient- and clinical-related factors were compared between the 2 groups. Kaplan-Meier and Cox proportional hazards regression models were used to assess overall survival. RESULTS: Of the patients studied, 18,346 (93.9%) had primary squamous cell carcinoma and 1193 (6.1%) had primary adenocarcinoma of the anus. The 5-year overall survival for stage II squamous cell carcinoma was 69.2%, and, for stage II adenocarcinoma, 5-year overall survival was 54.2% (p < 0.001). The 5-year overall survival for stage III squamous cell carcinoma was 55.2%, and, for stage III adenocarcinoma, 5-year overall survival was 32.9% (p < 0.001). On multivariable Cox regression, treatment with chemoradiation alone (HR, 0.67; p = 0.008) was associated with improved survival in squamous cell carcinoma. For the adenocarcinoma group, stage III disease (HR, 2.26; p < 0.001) and high tumor grade (HR, 1.59; p < 0.011) had a negative impact on survival, but there were no differences in survival based on the type of treatment received. LIMITATIONS: The National Cancer Database does not include information on specific chemotherapeutic or immunotherapy agents given to patients, nor does it provide the exact cause of death. CONCLUSIONS: Anal adenocarcinoma in comparison to anal squamous cell carcinoma had a lower 5-year overall survival stage for stage. Anal adenocarcinoma appears to be treated similarly to the rectal cancer paradigm, with frequent use of neoadjuvant chemoradiation. See Video Abstract at http://links.lww.com/DCR/B50. PATRONES DE EL CUIDADO Y COMPARACIÓN DE RESULTADOS ENTRE EL CARCINOMA DE CÉLULAS ESCAMOSAS ANAL PRIMARIO Y EL ADENOCARCINOMA ANAL: El tratamiento del adenocarcinoma del ano puede ser un desafío ya que hasta la fecha, hay pocos datos sobre los resultados y las tendencias en su tratamiento.Comparar y analizar los patrones de el cuidado y resultados de supervivencia de pacientes con carcinoma anal de células escamosas y adenocarcinoma anal.Este fue un estudio retrospectivo.Este estudio se realizó utilizando la Base de Datos Nacional de Cancer (National Cancer Database, NCB).Seleccionamos un total de 19,539 pacientes entre el 2004-2014 con carcinoma de células escamosas en estadio II-III o adenocarcinoma del ano.Los grupos de tratamiento analizados fueron solo cirugía, quimiorradiación neoadyuvante seguida por cirugía, cirugía seguida por quimiorradiación adyuvante o quimiorradiación definitiva.Se compararon los factores clínicos y de pacientes entre los dos grupos. Se utilizaron modelos de regresión de riesgos proporcionales de Kaplan-Meier y Cox para evaluar la supervivencia general.18,346 (93.9%) tenían carcinoma primario de células escamosas y 1,193 (6.1%) tenían adenocarcinoma primario del ano. La supervivencia global a 5 años para el carcinoma de células escamosas en estadio II fue del 69.2% y para el adenocarcinoma en estadio II fue del 54.2% (p < 0.001). La supervivencia global a cinco años para el carcinoma de células escamosas en estadio III fue del 55.2% y para el adenocarcinoma en estadio III fue del 32.9% (p < 0.001). En la regresión de Cox multivariable, el tratamiento con quimiorradiación sola (proporción de riesgo 0.67, p = 0.008) se asoció con una mejor supervivencia en el carcinoma de células escamosas. Para el grupo de adenocarcinoma, la enfermedad en estadio III (proporción de riesgo 2.26, p < 0.001) y el alto grado tumoral (proporción de riesgo 1.59, p < 0.011) tuvieron un impacto negativo en la supervivencia, pero no hubo diferencias en la supervivencia según el tipo de tratamiento recibido.La Base de Datos Nacional de Cancer no incluye información sobre agentes quimioterapéuticos o de inmunoterapia específicos que se administran a los pacientes, ni proporciona la causa exacta de la muerte.El adenocarcinoma anal en comparación con el carcinoma anal de células escamosas tuvo una supervivencia general inferior a 5 años, etapa por etapa. El adenocarcinoma anal parece tratarse de manera similar al paradigma del cáncer rectal, con el uso frecuente de quimiorradiación neoadyuvante. Vea el video del resumen en http://links.lww.com/DCR/B50.

Patterns of care and outcomes of intensity modulated radiation therapy versus three-dimensional conformal radiation therapy for anal cancer.

BACKGROUND: Definitive chemoradiation is the standard of care for anal squamous cell carcinoma. Compared to three-dimensional conformal radiation therapy (3DCRT), intensity modulated radiation therapy (IMRT) is increasingly becoming the preferred technique in order to reduce treatment related toxicity. The objective of this study is to evaluate practice patterns and total radiation treatment times of two radiation modalities. METHODS: A total of 6,966 patients with non-metastatic squamous cell carcinoma of the anus who received definitive chemoradiation were queried from the National Cancer Database (NCDB) from 2004-2013. Logistic regression was performed to assess for predictors of IMRT receipt. The Kaplan-Meier method and multivariable Cox regression analysis was used to assess overall survival (OS). RESULTS: In total, 3,868 (55.5%) received 3DCRT and 3,098 (44.5%) received IMRT. Total radiation treatment time was <7 weeks for 54.3% of patients treated with 3DCRT versus 63.8% of patients treated with IMRT. On multivariable logistic regression, positive clinical nodes (OR =1.20, P=0.001) and treatment at an academic facility (OR =1.23, P<0.001) were associated with increased likelihood of receiving IMRT. The 5-year OS was 73.0% for 3DCRT and 73.9% for IMRT (P=0.315). On multivariable analysis, total radiation treatment time ≥7 weeks (HR =1.33, P<0.001) was associated with worse survival while radiation modality (3DCRT vs. IMRT) did not impact survival (HR =0.98, P=0.763). CONCLUSIONS: IMRT has dramatically increased in utilization from 2% to 65% during the study time period. IMRT was less likely than 3DCRT to have prolonged radiation treatment times, which was associated with worse survival.

Clinical implications of PET/CT in prostate cancer management.

Several imaging modalities exist for the investigation of prostate cancer (PCa). From ultrasound to computed tomography (CT) and magnetic resonance imaging (MRI), the role of imaging in detecting lesion foci, staging, and localizing disease after biochemical recurrence (BCR) is expanding. However, many of the conventional imaging modalities are suboptimal, particularly in the detection of metastasis. Positron emission tomography (PET) has recently emerged as a promising tool in PCa management. The ability to develop radiolabeled tracers for functional imaging based on characteristics of PCa cells can potentially provide more insight into management by utilizing key features of those cells, such as metabolic activity, increased proliferation, and receptor expression. 18-flurodeoxyglucose (FDG) is one of the earliest tracers used in PET imaging that takes advantage of increased metabolism of glucose. Its role in PCa has been somewhat limited due to poor resolution and confounders including noise resulting from the proximity of the prostate to the bladder. Choline, a precursor molecule for a major component of the cell membrane, phosphatidylcholine, shows increased uptake in cells with rapid proliferation. When compared to metabolic based imaging techniques with FDG, choline PET/CT was superior. Nevertheless, choline PET/CT was not equivocal to MRI in detection of local disease, but was superior to conventional imaging in localizing metastasis and lymph node metastasis (LNM). Fluciclovine is another novel marker that utilizes the increased proliferation seen in tumor cells. Studies have shown it to be superior to choline PET/CT in PCa management, particularly in patients with BCR. As with choline PET/CT, studies that have assessed the impact of fluciclovine on clinical practice have highlighted the impact of these new tracers on clinical decision making. Most recently, the newest molecular probe targeting prostate specific membrane antigen (PSMA) was developed. It offers higher detection rates compared to choline PET/CT and conventional imaging modalities and has shown promise in LNM and BCR. With the wide range of available PET tracers, this review aims to highlight the role of each in lesion foci detection, primary staging, disease recurrence and explore the potential clinical impact.

Association of Nadir Prostate-specific Antigen >0.5 ng/mL after Dose-escalated External Beam Radiation with Prostate Cancer-specific Endpoints.

Objective Prior studies have suggested that prostate-specific antigen (PSA) nadir of 0.5 ng/mL is an important surrogate endpoint for prostate cancer-specific and all-cause mortality. This study analyzed our well-followed patient cohort to assess whether this endpoint was associated with differences in prostate cancer-specific endpoints in patients receiving dose-escalated radiation. Methods Patients with intermediate- or high-risk prostate cancer (≥T2b, or prostate-specific antigen >10 ng/mL, or Gleason score ≥7) who were treated with external beam radiation to a minimum dose of 7560 cGy +/- androgen deprivation between 2003 and 2011 were identified. Biochemical control, distant metastasis-free survival (DMFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were compared between those who achieved a nadir PSA ≤0.5 ng/mL with those who did not via Kaplan-Meier analysis. Univariable and multivariable Cox regression was performed on all endpoints to assess their impact on OS. Results There were 367 patients identified with a median follow-up of 99.5 months. Two hundred five patients (55.9%) received androgen deprivation for a median of 24 months (range 1-81 months). Most patients (n = 308, 83.9%) achieved a nadir PSA ≤0.5 ng/mL, which was associated with improvement across all endpoints at 10 years. This included biochemical control (68.0% versus 24.0%, p < 0.001), DMFS (89.6% versus 80.8%, p = 0.019), PCSS (91.1% versus 85.7%, p = 0.01), and OS (55.7% versus 45.8%, p = 0.048). On multivariable analysis, nadir PSA >0.5 ng/mL remained strongly associated with worse outcomes across all endpoints. Conclusions Achievement of nadir PSA ≤0.5 ng/mL after completion of dose-escalated radiation therapy was associated with improvement of all prostate cancer endpoints.

Patterns of stereotactic radiotherapy utilization and fractionation for acoustic neuroma in the United States.

OBJECTIVE: Stereotactic radiosurgery is a commonly offered modality utilized for the treatment of acoustic neuromas. In this study we sought to analyze the national practice patterns and utilization of GK compared to LINAC based radiosurgery. METHODS: Patients diagnosed with an acoustic neuroma between 2004-2013 and treated with LINAC or GK radiosurgery in 1-5 fractions were identified in the National Cancer Database. RESULTS: There were 2,705 patients analyzed, of which 2,222 (82.1%) received GK and 483 (17.9%) received LINAC based radiosurgery. Single fraction treatment was observed in 98.8% of GK patients, versus 19.5% of LINAC patients. LINAC based radiosurgery use increased from 3.5-3.7% in 2004-2005 to 15-26% from 2007-2013. On multivariable logistic regression the use of 3-5 fractions was strongly associated with LINAC based radiosurgery (p<0.001). CONCLUSION: GK remains the predominant modality for delivering radiosurgery to acoustic neuroma. LINAC based radiosurgery is being cautiously adopted and often utilizes a hypofractionated approach.

Patterns of care and outcomes of chemoradiation versus radiation alone for MGMT promoter unmethylated glioblastoma.

OBJECTIVE: The recommended treatment for O6-methylguanine-DNA methyltransferase (MGMT) promoter unmethylated glioblastoma (GBM) is radiation therapy with concurrent/adjuvant temozolomide (TMZ). However, it is well known that the clinical benefit from TMZ is lower in these patients. We sought to analyze patterns of care and outcomes of chemoradiation versus radiation alone in this cohort using a large, hospital database. PATIENTS AND METHODS: Patients diagnosed with MGMT promoter unmethylated GBM from 2010 to 2012 who received radiation (RT) or chemoradiation (CRT) were identified in the National Cancer Database. Logistic regression was performed to assess for predictors of receiving chemoradiation. The Kaplan-Meier method was used to assess overall survival (OS) by treatment group and Cox regression analysis was used to assess impact of covariates on OS. RESULTS: There were 738 patients who met the study criteria, of which 107 (14.5%) received RT alone and 631 (85.5%) received CRT with median RT dose 6000cGy for both groups. Median follow up for living patients was 21.9 months. Ninety-two (12.5%) patients did not undergo any resection, 330 (44.7%) underwent a subtotal resection and 316 (42.8%) had a gross total resection. The median and 2-year OS was 16.8 months and 24.7% for RT alone compared to 15.6 months and 25.9% for the CRT group (p = 0.250). On multivariable analysis, the addition of chemotherapy had no impact on survival (HR 1.12, 95% CI 0.86-1.46, p = 0.396). CONCLUSION: Despite the routine use of chemoradiation among patients with MGMT promoter unmethylated GBM, there does not appear to be a survival benefit compared to radiation alone.

Patterns of care and outcomes of adjuvant therapy for high-risk head and neck cancer after surgery.

BACKGROUND: Postoperative chemoradiotherapy (CRT) is considered standard of care in patients with locally advanced head and neck cancer with positive margins and/or extracapsular extension (ECE). METHODS: The National Cancer Data Base (NCDB) was queried to identify patients with squamous cell carcinoma of the head and neck with stages III to IVB disease or with positive margins and/or ECE diagnosed between 2004 and 2012 receiving postoperative radiotherapy (RT). Using univariable and multivariable logistic and Cox regression, we assessed for predictors of CRT use and covariables impacting overall survival (OS), including in a propensity-matched subset. RESULTS: Of 12 224 patients, 67.1% with positive margins and/or ECE received CRT as well as 54.0% without positive margins and/or ECE. The 5-year OS was 61.6% for RT alone versus 67.4% for CRT. In the propensity-matched cohort, OS benefit persisted with CRT, including in a subset with positive margins and/or ECE but not without. CONCLUSION: Postoperative CRT seems underutilized with positive margins and/or ECE and overutilized without positive margins and/or ECE. The CRT was associated with improved OS but the benefit persisted only in the subset with positive margins and/or ECE.

Characterization, treatment and outcomes of salivary ductal carcinoma using the National Cancer Database.

OBJECTIVES: To analyze clinical, treatment and outcome data for patients with salivary ductal carcinoma in a large population-based sample. MATERIALS AND METHODS: The National Cancer Database was queried to identify patients diagnosed with salivary ductal carcinoma between 2004 and 2013. Kaplan Meier and Cox regression analysis were used to assess overall survival (OS) and identify impact of specific variables on OS. RESULTS: A total of 495 patients were identified. The most common site of tumor origin was the parotid (80%). 130 patients (26.3%) presented with early stage (I-II) disease, 257 patients (51.9%) with locoregionally advanced pathologic stage (III-IVB) disease and 41 patients (8.3%) with metastatic disease. The 5year OS for these patients was 79.5%, 40.4% and 0% respectively. At presentation, 46.6% had node positive disease. Surgery was performed in 100% of patients with early stage disease, 98.4% with advanced disease and 90.2% with metastatic disease. Radiation therapy, generally postoperative radiation, was given to 58.5% of patients with stage I-II disease, 71.6% with stage III-IVB disease and 53.7% with metastatic disease. Chemotherapy was utilized in 5.4% of patients with stage I-II disease, 35% with stage III-IVB and 70.7% with metastatic disease. On multivariable analysis, there were no significant differences in OS based on receipt of adjuvant radiotherapy, chemotherapy, or chemoradiotherapy. CONCLUSION: Salivary ductal carcinoma represents an uncommon and aggressive subset of salivary tumors for which current adjuvant treatments do not have a detectable impact on overall survival.