Impact of environmental temperature on the survival outcomes of breast cancer: A SEER-based study.

BACKGROUND: Experimental evidence in tumor-bearing mouse models shows that exposure to cool, that is, sub-thermoneutral environmental temperature is associated with a higher tumor growth rate and an immunosuppressive tumor immune microenvironment than seen at thermoneutral temperatures. However, the translational significance of these findings in humans is unclear. We hypothesized that breast cancer patients living in warmer climates will have better survival outcomes than patients living in colder climates. METHODS: A retrospective population-based analysis was conducted on 270,496 stage I-III breast cancer patients, who were retrieved from the Surveillance, Epidemiology and End Results (SEER) over the period from 1996 to 2017. The average annual temperature (AAT) was calculated based on city level data from the National Centers for Environmental Information. RESULTS: A total of 270, 496 patients were analyzed. Temperature as assessed in quartiles. After adjusting for potential confounders, patients who lived in the 3rd and 4th quartile temperature regions with AAT 56.7-62.5°F (3rd quartile) and > 62.5°F (4th quartile) had a 7% increase in the OS compared to patients living at AAT < 48.5°F (1st quartile) (HR 0.93, 95% CI 0.90-0.95 and HR 0.93, 95% CI 0.91-0.96, respectively). For DSS, When comparing AAT quartiles, patients living with AAT in the range of 56.7-62.5°F and > 62.5°F demonstrated a 7% increase each in DSS after adjustment (HR 0.93, 95% CI 0.90-0.96 and HR 0.93, 95% CI 0.90-0.96). CONCLUSIONS: Higher environmental temperatures are associated with significantly better OS and DSS in breast cancer patients. Future research is warranted to confirm this observation using large datasets to elucidate the underlying mechanisms and investigate novel therapeutic strategies to minimize this geographic disparity in clinical outcomes.

Bevacizumab and gamma knife radiosurgery for first-recurrence glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common central nervous system malignancy in adults. Despite decades of developments in surgical management, radiation treatment, chemotherapy, and tumor treating field therapy, GBM remains an ultimately fatal disease. There is currently no definitive standard of care for patients with recurrent glioblastoma (rGBM) following failure of initial management. OBJECTIVE: In this retrospective cohort study, we set out to examine the relative effects of bevacizumab and Gamma Knife radiosurgery on progression-free survival (PFS) and overall survival (OS) in patients with GBM at first-recurrence. METHODS: We conducted a retrospective review of all patients with rGBM who underwent treatment with bevacizumab and/or Gamma Knife radiosurgery at Roswell Park Comprehensive Cancer Center between 2012 and 2022. Mean PFS and OS were determined for each of our three treatment groups: Bevacizumab Only, Bevacizumab Plus Gamma Knife, and Gamma Knife Only. RESULTS: Patients in the combined treatment group demonstrated longer post-recurrence median PFS (7.7 months) and median OS (11.5 months) compared to glioblastoma patients previously reported in the literature, and showed improvements in total PFS (p=0.015), total OS (p=0.0050), post-recurrence PFS (p=0.018), and post-recurrence OS (p=0.0082) compared to patients who received either bevacizumab or Gamma Knife as monotherapy. CONCLUSION: This study demonstrates that the combined use of bevacizumab with concurrent stereotactic radiosurgery can have improve survival in patients with rGBM.

Optimization of Radium-223 Treatment of Castration-resistant Prostate Cancer Based on the Burden of Skeletal Metastasis and Clinical Parameters.

BACKGROUND: Radium-223 dichloride (Ra-223) is now frequently used to treat prostate cancer that has metastasized to bone, although patient selection continues to be suboptimal for determining who will benefit most from this novel treatment modality. MATERIALS AND METHODS: Seventy-nine patients with metastatic castration-resistant prostate cancer (mCRPC) were treated with Ra-223 from 2012 to 2016. The burden of skeletal metastasis was determined for each using the Bone Scan Index (BSI) as a ratio of diseased to normal bone. Clinical, laboratory, and survival data were collected and examined for associations with BSI, and treatment tolerability was assessed. RESULTS: Chemotherapy-naïve patients were significantly more likely to complete the full course of treatment. Median follow-up was 31 months (range 0.7-38.8 months) and median overall survival was 15.4 months (range 9.5-20.6 months). Overall survival was significantly associated with findings on bone scans (P < .05). Patients with higher BSI tended toward poorer outcomes. Nearly half the patients with low baseline BSI survived 3 years or more following Ra-223 treatment. By contrast, only 20% of the patients with high baseline BSI lived for 1 year, and none lived for an additional 3. Baseline BSI was significantly associated with decreased hemoglobin, higher serum PSA and alkaline phosphatase levels, and treatment-associated reductions in platelet and absolute neutrophil counts. CONCLUSION: Our results suggest better outcomes to Ra-223 therapy for patients who are chemotherapy-naïve and who undergo treatment earlier in the course of their disease as reflected by low BSI and concordant laboratory parameters.

Effect of neighborhood deprivation index on breast cancer survival in the United States.

PURPOSE: To analyze the association between the Neighborhood Deprivation Index (NDI) and clinical outcomes of locoregional breast cancer (BC). METHODS: Surveillance, Epidemiology and End Results (SEER) database is queried to evaluate overall survival (OS) and disease-specific survival (DSS) of early- stage BC patients diagnosed between 2010 and 2016. Cox multivariate regression was performed to measure the association between NDI (Quintiles corresponding to most deprivation (Q1), above average deprivation (Q2), average deprivation (Q3), below average deprivation (Q4), least deprivation (Q5)) and OS/DSS. RESULTS: Of the 88,572 locoregional BC patients, 27.4% (n = 24,307) were in the Q1 quintile, 26.5% (n = 23,447) were in the Q3 quintile, 17% (n = 15,035) were in the Q2 quintile, 13.5% (n = 11,945) were in the Q4 quintile, and 15.6% (n = 13,838) were in the Q5 quintile. There was a predominance of racial minorities in the Q1 and Q2 quintiles with Black women being 13-15% and Hispanic women being 15% compared to only 8% Black women and 6% Hispanic women in the Q5 quintile (p < 0.001). In multivariate analysis, in the overall cohort, those who live in Q2 and Q1 quintile have inferior OS and DSS compared to those who live in Q5 quintile (OS:- Q2: Hazard Ratio (HR) 1.28, Q1: HR 1.2; DSS:- Q2: HR 1.33, Q1: HR 1.25, all p < 0.001). CONCLUSION: Locoregional BC patients from areas with worse NDI have poor OS and DSS. Investments to improve the socioeconomic status of areas with high deprivation may help to reduce healthcare disparities and improve breast cancer outcomes.

Clinicopathologic Predictors of Clinical Outcomes in Mammary Adenoid Cystic Carcinoma: A Multi-institutional Study.

Adenoid cystic carcinoma (AdCC) is an uncommon type of invasive breast carcinoma with a favorable prognosis. However, some cases are aggressive. The study aims to define the clinicopathologic predictors of outcome. Clinical, radiological, and pathologic variables were recorded for 76 AdCC cases from 11 institutions. The following histologic characteristics were evaluated by the breast pathologist in each respective institution, including Nottingham grade (NG), percentages of various growth patterns (solid, cribriform, trabecular-tubular), percentage of basaloid component, tumor borders (pushing, infiltrative), perineural invasion, lymphovascular invasion, necrosis, and distance from the closest margin. Various grading systems were evaluated, including NG, salivary gland-type grading systems, and a new proposed grading system. The new grading system incorporated the growth pattern (percent solid, percent cribriform), percent basaloid morphology, and mitotic count using the Youden index criterion. All variables were correlated with recurrence-free survival. Nineteen (25%) women developed local and/or distant recurrence. Basaloid morphology (≥25% of the tumor) was identified in 20 (26.3%) cases and a solid growth pattern (using ≥60% cutoff) in 22 (28.9%) cases. In the univariate analysis, the following variables were significantly correlated with worse recurrence-free survival: solid growth pattern, basaloid morphology, lymphovascular invasion, necrosis, perineural invasion, and pN-stage. In the multivariate analysis including basaloid morphology, pN-stage, lymphovascular invasion, and perineural invasion, basaloid morphology was statistically significant, with a hazard ratio of 3.872 (95% CI, 1.077; 13.924; P =.038). The NG and the new grading system both correlated with recurrence-free survival. However, grade 2 had a similar risk as grade 3 in the NG system and a similar risk as grade 1 in the new grading system. For solid growth patterns and basaloid morphology, using a 2-tier system with 1 cutoff was better than a 3-tier system with 2 cutoffs. Basaloid morphology and solid growth pattern have prognostic values for AdCC, with a 2-tier grading system performing better than a 3-tier system.

Perioperative Chemotherapy is Associated with Superior Overall Survival in Patients with Synchronous Colorectal Liver Metastases.

BACKGROUND: The sequence of localized and systemic treatment for colorectal liver metastases (CRLM) remains debated. Our objective is to analyze the effect of treatment sequence on overall survival (OS) in patients with CRLM using a large cancer database. PATIENTS AND METHODS: The national cancer database (NCDB) was utilized to identify patients with stage IV colorectal cancer (CRC) diagnosed between 2004 and 2016. OS was analyzed using standard univariate and multivariate methods. RESULTS: We identified 72,376 patients with synchronous CRLM, of whom 43,039 had liver-only metastases. Patients with liver-only CRLM had a median OS of 18.9 months, versus those with CRLM plus extrahepatic sites (11.3 months). In patients with liver-only CRLM, resection of both the primary and metastatic site was associated with median OS 38.9 months versus 30.2 months after resection of the metastatic site alone, and resection of the primary tumor alone (22.3 months, all p < 0.001). Receipt of perioperative chemotherapy correlated with a median OS of 44.7 months versus preoperative chemotherapy only (38.4 months) or postoperative chemotherapy only (27.9 months, all p < 0.001). Patients who received chemotherapy alone had a median OS of 16.4 months versus those who underwent resection without chemotherapy (9.5 months, p < 0.001). CONCLUSIONS: This study reveals a correlation between perioperative chemotherapy and superior OS in patients with liver-only CRLM, and shows that resection of the metastatic site was linked to better OS. Despite obvious cohort heterogeneity, the data can support a resection approach with additional, preferably peri- or preoperative systemic therapy for patients with CRLM.

Sequential Targeted Therapy for Advanced, Metastatic, and Recurrent Cervical Cancer: A Cost-Effectiveness Analysis of the Patient Journey.

OBJECTIVES: To evaluate outcomes and cost-effectiveness of targeted therapy sequencing for metastatic and recurrent cervical cancer. METHOD: Models were simulated based on phase II and III trials on bevacizumab (bev) from GOG-240, cemiplimab (cemi) from GOG 3016, pembrolizumab (pembro) from KEYNOTE-826, and tisotumab vedotin (tiso) from GOG 3023. Costs were based on IBM Micromedex RED BOOK™ and company listed costs. RESULTS: For [chemo + bev → chemo], total cost was $125,918.04, with median overall survival (mOS) of 21.8 months, and cost-effectiveness ratio (CER) of $119,835.79. For [chemo + bev → cemi], total cost was $187,562.99 with mOS of 28.5 months and CER of $162,039.16. For [chemo + bev + pembro → chemo], total cost was $319,963.78 with mOS 32.9 months and CER of $249,930.10. For [chemo + bev + pembro → tiso], total cost was $455,204.45, with mOS 36.5 months and CER of $320,072.99. CONCLUSION: The combination of immunotherapies and biologics have significantly increased overall survival, but with associated higher costs, primarily related to drug costs.

Development and validation of nomogram to improve the specificity of multiparametric MRI for clinically significant prostate cancer.

OBJECTIVE: To develop and validate a nomogram to improve the specificity of prostate imaging reporting and data system (PI-RADS) on multiparametric magnetic resonance imaging (MRI) for clinically significant prostate cancer on targeted fusion biopsy. METHODS: A retrospective review of patients who underwent fusion biopsy for PI-RADS 3-5 lesions using UroNav and Artemis systems between 2016 and 2022 was performed. Patients were divided into those with CS disease on fusion biopsy (Gleason grade group ≥2) versus those without. Multivariable analysis was used to identify variables associated with CS disease. A 100-point nomogram was constructed, and ROC curve was generated. RESULTS: 1485 lesions (1032 patients) were identified, 510 (34%) were PI-RADS 3, 586 (40%) were PI-RADS 4, and 389 (26%) were PI-RADS 5. Of these, 11% of PI-RADS 3, 39% of PI-RADS 4, and 61% of PI-RADS 5 showed CS disease. CS disease was associated with older age (OR 1.04, 95% CI 1.02-1.06, p < 0.01), previous negative biopsy (OR 0.52, 95% CI 0.36-0.74, p < 0.01), presence of multiple PI-RADS 3-5 lesions (OR 0.61, 95% CI 0.45-0.83, p < 0.01), peripheral zone location (OR 1.88, 95% CI 1.30-2.70, p < 0.01), PSA density (OR 1.48 per 0.1 unit, 95% CI 1.33-1.64, p < 0.01), PI-RADS score 4 (OR 3.28, 95% CI 2.21-4.87, p < 0.01), and PI-RADS score 5 (OR 7.65, 95% CI 4.93-11.85, p < 0.01). Area under ROC curve was 82% for nomogram compared to 75% for PI-RADS score alone. CONCLUSION: We report a nomogram that combines PI-RADS score with other clinical parameters. The nomogram outperforms PI-RADS score for the detection of CS prostate cancer.

Adapting Community Educational Programs During the COVID-19 Pandemic: Comparing the Feasibility and Efficacy of a Lung Cancer Screening Educational Intervention by Mode of Delivery.

Few eligible patients receive lung cancer screening. We developed the Lung AIR (awareness, information, and resources) intervention to increase community education regarding lung cancer screening. The intervention was designed as an in-person group intervention; however, the COVID-19 pandemic necessitated adapting the mode of delivery. In this study we examined intervention feasibility and efficacy overall and by mode of delivery (in-person group vs. one-on-one phone) to understand the impact of adapting community outreach and engagement strategies. Feasibility was examined through participant demographics. Efficacy was measured through pre/post knowledge, attitudes, and beliefs about lung cancer screening, and intention to complete screening. We reached N = 292 participants. Forty percent had a household income below $35,000, 58% had a high school degree or less, 40% were Hispanic, 57% were Black, and 84% reported current or past smoking. One-on-one phone sessions reached participants who were older, had lower incomes, more current smoking, smoked for more years, more cigarettes per day, lower pre-intervention lung cancer screening knowledge, and higher pre-intervention fear and worry. Overall pre/post test scores show significant increases in knowledge, salience, and coherence, and reduced fear and worry. Participants in the one-on-one phone sessions had significantly higher increases in salience and coherence and intention to complete screening compared to participants in the in-person group sessions. The Lung AIR intervention is a feasible and effective community-based educational intervention for lung cancer screening. Findings point to differences in reach and efficacy of the community-based intervention by mode of delivery.

CD40 and CD80/86 signaling in cDC1s mediate effective neoantigen vaccination and generation of antigen-specific CX3CR1+ CD8+ T cells.

The use of tumor mutation-derived neoantigen represents a promising approach for cancer vaccines. Preclinical and early phase human clinical studies have shown the successful induction of tumor neoepitope-directed responses; however, overall clinical efficacy of neoantigen vaccines has been limited. One major obstacle of this strategy is the prevailing lack of sufficient understanding of the mechanism underlying the generation of neoantigen-specific CD8+ T cells. Here, we report a correlation between antitumor efficacy of neoantigen/toll-like receptor 3 (TLR3)/CD40 agonists vaccination and an increased frequency of circulating antigen-specific CD8+ T cells expressing CX3C chemokine receptor 1 (CX3CR1) in a preclinical model. Mechanistic studies using mixed bone marrow chimeras identified that CD40 and CD80/86, but not CD70 signaling in Batf3-dependent conventional type 1 dendritic cells (cDC1s) is required for the antitumor efficacy of neoantigen vaccine and generation of neoantigen-specific CX3CR1+ CD8+ T cells. Although CX3CR1+ CD8+ T cells exhibited robust in vitro effector function, in vivo depletion of this subset did not alter the antitumor efficacy of neoantigen/TLR3/CD40 agonists vaccination. These findings indicate that the vaccine-primed CX3CR1+ subset is dispensable for antitumor CD8+ T cell responses, but can be used as a blood-based T-cell biomarker for effective priming of CD8+ T cells as post-differentiated T cells. Taken together, our results reveal a critical role of CD40 and CD80/86 signaling in cDC1s in antitumor efficacy of neoantigen-based therapeutic vaccines, and implicate the potential utility of CX3CR1 as a circulating predictive T-cell biomarker in vaccine therapy.

Tumor-associated mononuclear cells in the tumor bed of triple-negative breast cancer associate with clinical outcomes in the post-neoadjuvant chemotherapy setting.

PURPOSE: To evaluate the clinical role of tumor-associated macrophages, including foamy (FM) and hemosiderin-laden macrophages (HLM) in the tumor bed (TB) of triple-negative breast cancer (TNBC) post-neoadjuvant chemotherapy (NACT). METHODS: We conducted a pathologic review of 129 women, diagnosed with TNBC between 2002 and 2016 at our institute. The residual cancer burden (RCB) was calculated. We estimated the percentage of tumor-infiltrating lymphocytes (TILs) in the core needle biopsy (CNB), and FM, HLM, and TILs (in TB) [the combined cells are designated as tumor-associated mononuclear cells (TAMNC)]. The information on patient demographics, chemotherapy regimen, recurrence-free survival (RFS), and overall survival (OS) was extracted from the medical records. RESULTS: Pathologic complete response (pCR) was achieved in 34.1% of the women. TILs (10% increment in CNB) only were associated with pCR in the multivariable analysis [odds ratio 1.04 (1.02, 1.06) (p = 0.0003)]. Immune cells associated with better OS included TAMNC (≤ 30%) [hazard ratio (HR) 4.32 (1.93, 9.66) (p = 0.0004)], and FM (0%) [HR 2.30 (1.06, 4.98) (p = 0.036)]. While increased HLM (10% increment) was statistically significant with HR 0.93 and 95% CI (0.88 to 0.98) (p = 0.0061), using a cutoff of 0%, HLM (0%: negative vs. ≥ 1%: positive) achieved only borderline significance with HR 2.05 (0.98, 4.31) (p = 0.058). Similarly, these immune cells were also associated with better RFS: TAMNC (≤ 30%) [HR 4.57 (2.04, 10.21) (p = 0.0002)], FM (0%) [HR 2.80 (1.23, 6.35) (p = 0.014)], and HLM (0%) [HR 2.34 (1.07, 5.11) (p = 0.03)]. TILs (in TB) were not associated with any clinical outcomes. CONCLUSIONS: Although TILs may play a role in the response to NACT, they may not be critical to the prognosis after NACT. Instead, FM and HLM may assume this role. More studies are warranted.

Lack of racial differences in clinical outcomes of breast cancer patients receiving neoadjuvant chemotherapy: a single academic center study.

PURPOSE: To examine the association between race and clinical outcomes (pathological complete response [pCR]; recurrence-free survival [RFS], and overall survival [OS]) in patients diagnosed with triple-negative (TNBC) or HER2-positive breast cancer treated with neoadjuvant chemotherapy (NAC). METHODS: Patients who self-identified as non-Hispanic white (NHW) or non-Hispanic Black (NHB) and were diagnosed with Stage I-III TNBC (n = 171 including 124 NHW and 47 NHB) and HER2-positive (n = 161 including 136 NHW and 25 NHB) breast cancer who received NAC from 2000 to 2018 at Roswell Park Comprehensive Cancer Center were included. Associations of race with pCR and survival outcomes were evaluated using logistic and Cox regression models, respectively. RESULTS: There was no statistically significant difference in pCR between NHB and NHW patients with TNBC (31.9 vs 29.8%; OR: 1.11, 95% CI 0.54-2.29) or HER2-positive breast cancer (36.0 vs 39.7%; OR: 0.87, 95% CI 0.36-3.11). After controlling for potential confounders, including age, stage, treatment regimens, insurance status, and comorbidities, no statistically significant difference in OS or RFS was observed between NHB and NHW patients within either subtype. CONCLUSION: TNBC or HER2-positive breast cancer patients treated at a single academic center in Buffalo, NY, showed similar outcomes independent of patients' race. Given the known genetic diversity of African American ancestry in the US, further studies investigating the interplay between race, geography, and clinical outcomes are warranted.

Restrictive Intraoperative Fluid Rate is Associated with Improved Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Management of patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CS/HIPEC) has historically favored liberal fluid administration owing to lengthy duration of surgery and hyperthermia. This practice has been challenged in recent years with studies demonstrating improved outcomes with restrictive fluid administration. METHODS: Patients who underwent CS/HIPEC between March 2010 and September 2018 were included for analysis. Patients who received an above-median fluid rate (high-IVF) versus below-median fluid rate (low-IVF) were compared, and multivariate analyses were performed for length of stay, 90-day unplanned readmissions, and major complications. RESULTS: The 167 patients had a mean age of 56.7 ± 11.4 years and body mass index of 29.5 ± 6.9 kg/m2. The median rate of total intraoperative crystalloid and colloid was 7.4 mL/kg/h. The low-IVF group had less blood loss (183 vs. 330 mL, p = 0.002), were less likely to need intraoperative vasopressor drip (2.4% vs. 11.9%, p = 0.018), and experienced fewer cardiac complications (2.4% vs. 10.7%, p = 0.031), pneumonias (0% vs. 6.0%, p = 0.024), and Clavien-Dindo grade 3-5 complications (14.5% vs. 33.3%, p = 0.004). Multivariate analyses identified bowel resection (HR 4.65, p = 0.0008) as a risk factor for 90-day unplanned readmission, while bowel resection, intraoperative fluid rate, and estimated blood loss were associated with increased length of stay. CONCLUSION: Higher intraoperative fluid intake was associated with multiple postoperative complications and increased length of stay, and represents a potentially avoidable risk factor for morbidity in CS/HIPEC.

Incidence trends and survival analysis of atypical meningiomas: a population-based study from 2004 to 2018.

PURPOSE: Atypical meningiomas have histologic and clinical features that fall between those for benign and malignant meningiomas. The incidence of atypical meningiomas has not been well studied with respect to changes in the World Health Organization (WHO) classification scheme over time. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database was queried to obtain data from 2004 to 2018 for patients with all meningiomas, including atypical. Age-adjusted incidence rates were generated and annual percent change (APC) in the incidence rates was calculated with joinpoint regression. Survival was analyzed using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: A total of 4476 patients diagnosed with meningioma were identified from the SEER 18 registries. The incidence of atypical meningioma increased at an APC of 5.6% [95% confidence interval [CI], 3.4-7.8]; significantly faster than all meningiomas, which rose at an APC of 2.5% (95%CI 1.8-3.1;p = 0.008). For atypical meningiomas, the 1, 3, 5, and 10-year survival rates were 91.9%, 81.3%, 68.8%, and 34.3%, respectively. Male sex, older age (≥ 60 years), and large tumor size (> 5 cm) were independent risk factors for an unfavorable prognosis. CONCLUSIONS: The incidence of atypical meningioma was observed to be increasing relative to all meningiomas. It is important to diligently monitor atypical meningioma incidence and mortality rates over time to see whether observed uptrends persist. Continued effort toward improving outcomes in patients with atypical meningiomas is warranted, especially in light of an apparent rise in incidence.

Human papillomavirus vaccination uptake among childhood cancer survivors in Western New York.

INTRODUCTION: The risk of human papillomavirus (HPV)-associated cancers is significantly higher among survivors of a childhood cancer compared to the general population. Despite this, their HPV vaccine uptake rates are lower. We examined factors related to HPV vaccine uptake among childhood cancer survivors from Western New York over 13 years following the introduction of HPV vaccines. METHODS: Retrospective review of patients diagnosed with invasive or noninvasive cancerous conditions at age 9 or younger treated at Roswell Park Oishei Children's Cancer and Blood Disorder Program. We matched vaccine date information for patients aged 9-26 years between 2006 and 2020 from the New York State Immunization Information System. Demographic and cancer-related information was abstracted from electronic medical records. Cumulative vaccine uptake was assessed by Kaplan-Meier and Cox proportional hazards regression models. RESULTS: A total of 284 patients were included in the analyses. Most were non-Hispanic/White (80.3%) and resided in a metropolitan area (81.7%). Approximately half had leukemia or lymphoma (54.9%), and most received chemotherapy. Females were more likely to initiate the HPV vaccine and did so sooner (median = 5.5 years) than males (median = 5.7 years; log-rank p = .301). Patients who were older at vaccine eligibility and males who received blood product transfusions were significantly less likely to initiate the HPV vaccine. CONCLUSION: While rates of HPV vaccine initiation have been increasing with time among childhood cancer survivors, they remain low overall, with differences seen by treatment and diagnosis. Our findings support the need for further research to optimize HPV vaccine delivery in cancer care.

Acute gastric conduit dilation after minimally invasive esophagectomy: a 10-year experience.

Despite decreasing overall morbidity with minimally invasive esophagectomy (MIE), conduit functional outcomes related to delayed emptying remain challenging, especially in the immediate postoperative setting. Yet, this problem has not been described well in the literature. Utilizing a single institutional prospective database, 254 patients who underwent MIEs between 2012 and 2020 were identified. Gastric conduit dilation was defined as a conduit occupying >40% of the hemithorax on the postoperative chest X-ray. Sixty-seven patients (26.4%) demonstrated acute conduit dilation. There was a higher incidence of conduit dilation in the patients who underwent Ivor Lewis esophagectomy compared to those with a neck anastomosis (67.2% vs. 47.1%; P = 0.03). Patients with dilated conduits required more esophagogastroduodenoscopies (EGD) (P < 0.001), conduit-related reoperations within 180 days (P < 0.001), and 90-day readmissions (P = 0.01). Furthermore, in 37 patients (25.5%) undergoing Ivor Lewis esophagectomy, we returned to the abdomen after intrathoracic anastomosis to reduce redundant conduit and pexy the conduit to the crura. While conduit dilation rates were similar, those who had intraabdominal gastropexy required EGD significantly less and trended toward a lower incidence of conduit-related reoperations (5.6% vs. 2.7%). Multivariable analysis also demonstrated that conduit dilation was an independent predictor for delayed gastric conduit emptying symptoms, EGD within 90 days, conduit-related reoperation within 180 days, and 30-day as well as 90-day readmission. Patients undergoing MIE with acute gastric conduit dilation require more endoscopic interventions and reoperations.

Robotic versus thoraco-laparoscopic minimally invasive Ivor Lewis esophagectomy, a matched-pair single-center cohort analysis.

Minimally invasive esophagectomy (MIE) is becoming more widespread with a documented improvement in postoperative morbidity based on level I evidence. However, there is a lack of consensus regarding the optimal MIE approach, conventional thoracoscopy/laparoscopy vs robotics as well as the ideal anastomotic technique. All patients who underwent MIE via an Ivor Lewis approach with a side-to-side stapled anastomosis were included. The thoracoscopy-laparoscopy (TL) group was compared to the robotic group with respect to perioperative outcomes using the entire cohorts and after 1:1 propensity score matching. Comparisons were made using the Mann-Whitney U and Fisher's exact tests. Between July 2013 and November 2020, 72 TL and 67 robotic Ivor Lewis MIE were performed. After comparing the two unadjusted cohorts and 51 propensity matched pairs, there was a decrease in Clavien-Dindo Grade 2 or above complications in the robotic vs TL group (59.7% vs 41.8% [P = 0.042], (62.7% vs 39.2% [P = 0.029]), respectively. In both analyses, there was a reduction in hospital length of stay (median of 8 vs 7 days, P < 0.001) and a trend toward less anastomotic leaks in the robotic group (Unadjusted: 12.5 vs 3% [P = 0.057], Propensity-matched analysis: 13.7% vs 3.9% [P = 0.16]), respectively. A clinically significant decrease in overall morbidity, cardiac complications and hospital length of stay was observed in the robotic Ivor Lewis cohort when compared with the TL group at a high volume MIE program. Side-to-side stapled thoracic anastomoses utilizing a robotic platform provides the best outcomes in this single institution experience.

Practical and robust test for comparing binomial proportions in the randomized phase II setting.

The one-arm, non-randomized, one/two-stage phase II designs have been a mainstay in oncology trials for evaluating response rates or similar variants (i.e., tests about single proportions). With the goal of screening new therapies that have the potential to move into a randomized phase III trial or a subsequent randomized phase II trial, all while maintaining a logistically feasible sample size. However, since the implementation of the Food and Drug Administration's Fast Track Designation, there has been a trend toward randomized phase II clinical trials as a source of stronger evidence for those seeking fast-track approvals. While there are many single- and multi-stage randomized designs for evaluating proportions in this phase II setting, there still exist limitations in terms of sample size (which directly impacts cost and study duration) or operating characteristics (ex. maintained type I error). In this article, we propose a new test for comparing two binomial proportions, which is a modification across existing methods (the standard z-test and Jung's test). This approach is contrasted with existing methods via numeric evaluation and further contrasted using a real-world oncology trial. The proposed method demonstrates improvements in efficiency and robustness against deviations from design assumptions. When applied to the existing trial, significant savings with respect to cost and time are illustrated. Our proposed test for comparing binomial proportions provides an efficient and robust alternative in the randomized phase II oncology setting, especially when the control arm has a high rate.

A phase I study of the anaplastic lymphoma kinase inhibitor ceritinib in combination with gemcitabine-based chemotherapy in patients with advanced solid tumors.

In this phase I, dose-escalation study, we sought to determine the maximum tolerated dose (MTD) of the anaplastic lymphoma kinase/c-ROS oncogene 1 receptor (ALK/ROS1) inhibitor ceritinib in combination with gemcitabine-based chemotherapy in patients with advanced solid tumors. Secondary objectives were characterization of the safety profile, pharmacokinetics and preliminary efficacy of these combinations, and identification of potential biomarkers of efficacy. Ceritinib was combined with gemcitabine (Arm 1), gemcitabine/nab-paclitaxel (Arm 2) or gemcitabine/cisplatin (Arm 3). Drug concentrations in plasma were measured by tandem mass spectrometric detection (LC-MS/MS). We analyzed archival tumor tissue for ALK, ROS1, hepatocyte growth factor receptor (c-MET) and c-Jun N-terminal kinase (JNK) expression by immunohistochemistry. Arm 2 closed early secondary to toxicity. Twenty-one patients were evaluable for dose-limiting toxicity (DLT). There was one DLT in Arm 1 (grade 3 ALT increase) and three DLTs in Arm 3 (grade 3 acute renal failure, grade 3 thrombocytopenia, grade 3 dyspnea). The MTD of ceritinib was determined to be 600 mg (Arm 1) and 450 mg orally daily (Arm 3). Main toxicities were hematologic, constitutional and gastrointestinal as expected by the chemotherapy backbone. The apparent clearance for ceritinib decreased substantially after repeated dosing; cisplatin did not significantly affect the pharmacokinetics of ceritinib. The overall response rate was 20%; the median progression-free survival was 4.8 months. Three out of five response-evaluable cholangiocarcinoma patients had clinical benefit. Increased expression of c-MET was associated with a lack of clinical benefit. Ceritinib in combination with gemcitabine and gemcitabine/cisplatin has a manageable toxicity profile. Further development of this strategy in tumors with ALK or ROS1 fusions is warranted.

Oncologic outcome of radical prostatectomy versus radiotherapy as primary treatment for high and very high risk localized prostate cancer.

OBJECTIVE: To compare the oncologic outcomes of radical prostatectomy (RP) versus external beam radiotherapy (EBRT) ± androgen deprivation therapy for primary treatment of high risk localized prostate cancer (CaP). METHODS: We retrospectively reviewed a prospectively-populated database for cases who underwent primary treatment for high risk localized CaP, had more than 2 years follow-up, and were treated since 2006. A total of 335 cases were studied of whom 291 underwent RP and 44 underwent EBRT. Clinical characteristics, biochemical progression-free survival (BPFS), metastasis-free survival (MFS), cancer-specific survival (CSS) and overall survival (OS) were compared. RESULTS: EBRT cases were older (p < .01; mean 71 years vs. 61 years) and had longer PSA doubling time (PSADT) (p = .03; median 4.8 years vs. 3.5 years) than RP. Race, pretreatment PSA and biopsy Gleason score were similar. Median follow-up was 5.1 (range: 2.3-12.8) years for RP versus 3.3 (range: 2-12.4) years for EBRT. Three- and 5-year BPFS were 42% and 36% after RP versus 86% and 75% after EBRT (p < .01). The rate of adjuvant/salvage therapy was 58% after RP versus 20% after EBRT (p < .01). Three- and 5-year MFS were 80% and 77% after RP versus 91% and 91% after EBRT (p = .11). Three-year CSS was 98% in both groups and OS was 97% after RP versus 94% after EBRT (p = .73). CONCLUSIONS: RP had higher rates of biochemical failure and adjuvant or salvage treatment versus EBRT in high risk localized CaP. MFS trended toward benefit after EBRT, but CSS and OS remained high in both groups.