Association between diabetes and subsequent malignancy risk among older breast cancer survivors.

Type II diabetes is associated with cancer risk in the general population but has not been well studied as a risk factor for subsequent malignancies among cancer survivors. We investigated the association between diabetes and subsequent cancer risk among older (66-84 years), 1-year breast cancer survivors within the linked Surveillance Epidemiology and End Results (SEER)-Medicare database using Cox regression analyses to quantify hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Among 133 324 women, 29.3% were diagnosed with diabetes before or concurrent with their breast cancer diagnosis, and 10 452 women developed subsequent malignancies over a median follow-up of 4.3 years. Diabetes was statistically significantly associated with liver (HR = 2.35, 95% CI = 1.48 to 3.74), brain (HR = 1.94, 95% CI = 1.26 to 2.96), and thyroid cancer risks (HR = 1.38, 95% CI = 1.01 to 1.89). Future studies are needed to better understand the spectrum of subsequent cancers associated with diabetes and the role of diabetes medications in modifying subsequent cancer risk, alone or in combination with cancer treatments.

Short course radiotherapy versus radiochemotherapy for locally advanced rectal cancers in the elderly (UNICANCER PRODIGE 42/GERICO 12 study): Quality of life and comprehensive geriatric assessment.

BACKGROUND: The results of the PRODIGE 42/GERICO 12 study showed that short course radiotherapy had a better tolerance profile than radiochemotherapy, with comparable oncological results. We have included Quality of Life analyses and oncogeriatric evaluations in this study. PATIENTS AND METHODS: In all, 101 patients ≥75 years of age with resectable T3-T4 rectal adenocarcinoma less than 12 cm from the anal margin received short course radiotherapy (5X5 Gy in one week) or radiochemotherapy (50 Gy, 2 y/f and capecitabine 800 mg/m2, 5 days/week) with delayed surgery (7 weeks ± 1) in both groups. The Quality of Life analyses (EORTC QLQ C-30 et ELD14) were conducted upon inclusion, pre-operatively, at 3, 6 and 12 months post-op, together with the oncogeriatric evaluations, including an evaluation of the IADL and ADL scores, walking speed, GDS15, MMSE, MNA. RESULTS: We did not highlight any statistical difference for the global EORTC QLQ-C30 score; several factors are statistically in favor of the short course radiotherapy group at 3 months post-op (cognitive functions, fatigue, appetite). In the case of the ELD14 score, the disease burden is perceived as more negative at 3, 6 and 12 months postop in the radiochemotherapy group. The IADL score deteriorated in 44.8 % of the radiochemotherapy group and 14.8 % of the radiotherapy group (p = 0.032); similarly, the GDS15 depression score was better preserved in the short course radiotherapy group (p = 0.05). An analysis of the other scores: ADL, walking speed, MNA, MMSE did not highlight any statistical difference. CONCLUSION: Short course radiotherapy achieves better results in terms of Quality of Life and preservation of autonomy in patients aged ≥75 treated for locally advanced rectal cancer.

Financial toxicity among people with metastatic cancer: findings from the Cancer Experience Registry.

PURPOSE: This study describes financial toxicity (FT) reported by people with metastatic cancer, characteristics associated with FT, and associations between FT and compensatory strategies to offset costs. METHODS: Cancer Support Community's Cancer Experience Registry data was used to identify respondents with a solid tumor metastatic cancer who completed the Functional Assessment of Chronic Illness Therapy COmprehensive Score for Financial Toxicity (FACIT-COST) measure. Multivariable logistic regression analyses examined associations between respondent characteristics and FT, and FT and postponing medical visits, nonadherence to medications, and postponing supportive and/or psychosocial care. RESULTS: 484 individuals were included in the analysis; the most common cancers included metastatic breast (31%), lung (13%), gynecologic (10%), and colorectal (9%). Approximately half of participants (50.2%) reported some degree of FT. Those who were non-Hispanic White, Hispanic, or multiple races (compared to non-Hispanic Black), and who reported lower income, less education, and being less than one year since their cancer diagnosis had greater odds of reporting FT. Individuals with any level of FT were also more likely to report postponing medical visits (Adjusted Odds Ratio [OR] 2.58; 95% Confidence Interval [CI] 1.45-4.58), suboptimal medication adherence (Adjusted OR 5.05; 95% CI 2.77-9.20) and postponing supportive care and/or psychosocial support services (Adjusted OR 4.16; 95% CI 2.53-6.85) compared to those without FT. CONCLUSIONS: With increases in the number of people living longer with metastatic cancer and the rising costs of therapy, there will continue to be a need to systematically screen and intervene to prevent and mitigate FT for these survivors.

Assessment of second primary malignancies among treated and untreated patients with chronic lymphocytic leukemia using real-world data from the USA.

Aim: Improved management of chronic lymphocytic leukemia (CLL) has resulted in a growing population of CLL survivors; these patients have a higher risk of developing second primary malignancies (SPMs) versus the general population. This retrospective cohort study aims to assess the timing, frequency, incidence and types of SPMs in treated and untreated patients with CLL in the USA, using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links a nationally representative cancer registry with Medicare claims data. Patients & methods: Patients aged ≥66 years with newly diagnosed CLL between 1 January 2010 and 31 December 2016, who were enrolled in Parts A and B of Medicare for ≥12 months pre-diagnosis of CLL were selected from the database. Patients were assessed for ≥36 months until the end of continuous enrollment in Medicare Parts A, B and D, a switch to a health maintenance organization, death, or end of the study period (December 2019). Results: Of 3053 patients included in the analyses, 620 (20.3%) were treated and 2433 (79.7%) were untreated within 36 months of diagnosis. Overall, 638 (20.9%) patients developed a SPM, 26.8% of patients in the treated cohort and 19.4% of patients in the untreated cohort. The most common SPMs for both cohorts were squamous cell carcinoma and acute myeloid leukemia. Among the 166 treated patients who developed a SPM, a greater proportion developed their first SPM after treatment initiation versus those who developed their first SPM prior to treatment initiation (p < 0.001). A significantly lower percentage of patients who received targeted therapy developed a SPM (p < 0.05) versus patients treated with anti-CD20 + chemotherapy. Conclusion: Findings indicate that treatment type and timing can affect SPM development in patients with CLL. Combined with previous findings, this can help inform best practices in monitoring for SPM in patients with CLL.

Secondary cancer risk assessments following the proton therapy of lung cancer as the functions of field characteristics and patient age.

INTRODUCTION: Radiation-induced secondary cancers relevant to proton therapy are still a main concern among cancer survivors. This study aims to determine the effects of age at exposure and treatment field size on radiation-induced secondary tumors following the proton therapy of lung cancer within out of field organs through the Monte Carlo (MC) simulation approach. MATERIAL AND METHODS: A full MC model of ICRP-110 male phantom was simulated to calculate the absorbed dose corresponding to secondary radiations within distant organs from the tumor volume. Then, the risks of secondary malignancies were estimated by employing the recommended risk model by the Committee of Biological Effects of Ionizing Radiation (BEIR) for different treatment field sizes and various patient ages at exposure. RESULTS: The results revealed that by increasing the patient age from 25 to 45 years, lifetime attributable risk (LAR) values were decreased. Maximum and minimum mortality rates were obtained for the liver and thyroid at the fixed age of 25 years, respectively. Calculated risk values for most near organs to the tumor were higher than those for distant organs. Changing the aperture size from 5 × 5 cm2 to 8 × 10 cm2 resulted in LAR increments with maximum variations of 12.5% for the stomach and a rough variation of 1.12 times in LAR for all exposure ages. CONCLUSION: Our work on whole-body phantom addresses the impact of age at exposure and aperture size on LAR during the proton therapy of lung cancer. To minimize secondary cancer risks relevant to proton therapy of lung cancer, extra attention should be considered.

Trends in new and persistent opioid use in older adults with and without cancer.

BACKGROUND: The impact of ongoing efforts to decrease opioid use on patients with cancer remains undefined. Our objective was to determine trends in new and additional opioid use in patients with and without cancer. METHODS: This retrospective cohort study used data from Surveillance, Epidemiology, and End Results program-Medicare for opioid-naive patients with solid tumor malignancies diagnosed from 2012 through 2017 and a random sample of patients without cancer. We identified 238 470 eligible patients with cancer and further focused on 4 clinical strata: patients without cancer, patients with metastatic cancer, patients with nonmetastatic cancer treated with surgery alone ("surgery alone"), and patients with nonmetastatic cancer treated with surgery plus chemotherapy or radiation therapy ("surgery+"). We identified new, early additional, and long-term additional opioid use and calculated the change in predicted probability of these outcomes from 2012 to 2017. RESULTS: New opioid use was higher in patients with cancer (46.4%) than in those without (6.9%) (P < .001). From 2012 to 2017, the predicted probability of new opioid use was more stable in the cancer strata (relative declines: 0.1% surgery alone; 2.4% surgery+; 8.8% metastatic cancer), than in the noncancer stratum (20.0%) (P < .001 for each cancer to noncancer comparison). Early additional use declined among surgery patients (‒14.9% and ‒17.5% for surgery alone and surgery+, respectively) but was stable among patients with metastatic disease (‒2.8%, P = .50). CONCLUSIONS: Opioid prescribing declined over time at a slower rate in patients with cancer than in patients without cancer. Our study suggests important but tempered effects of the changing opioid climate on patients with cancer.

Oligo-Metastatic Disease in Oncology: Exploring the Limits and the Potential of Genetic Assessment.

Oligo-metastatic disease (OMD) in the field of oncology denotes a distinct subset of metastatic tumors characterized by less aggressive biological behavior and extended survival times in comparison to their widely metastatic counterparts. While there is a general consensus regarding the existence of OMD, there remains a lack of widely accepted criteria for its a priori identification at the time of presentation. This review delves into the concept of OMD, placing a particular emphasis on the significance of understanding the limitations and potential of genetic assessments. It explores how these aspects are crucial in advancing our comprehension of this phenomenon. In a rapidly advancing era of precision medicine, understanding the intricacies of OMD opens up exciting possibilities for tailored treatment approaches. By elucidating the genetic underpinnings and dynamic nature of this condition, we stand to improve patient outcomes and potentially shift the paradigm of metastatic cancer management.

Interpretable machine learning accurately reclassifies lobectomy surgical approaches by cost.

BACKGROUND: The volume of robotic lung resection continues to increase despite its higher costs and unproven superiority to video-assisted thoracoscopic surgery. We evaluated whether machine learning can accurately identify factors influencing cost and reclassify high-cost operative approaches into lower-cost alternatives. METHODS: The Florida Agency for Healthcare Administration and Centers for Medicare and Medicaid Services Hospital and Physician Compare datasets were queried for patients undergoing open, video-assisted thoracoscopic surgery and robotic lobectomy. K-means cluster analysis was used to identify robotic clusters based on total cost. Predictive models were built using artificial neural networks, Support Vector Machines, Classification and Regression Trees, and Gradient Boosted Machines algorithms. Models were applied to the high-volume robotic group to determine patients whose cost cluster changed if undergoing a video-assisted thoracoscopic surgery approach. A local interpretable model-agnostic explanation approach personalized cost per patient. RESULTS: Of the 6,618 cases included in the analysis, we identified 4 cost clusters. Application of artificial neural networks to the robotic subgroup identified 1,642 (65%) cases with no re-assignment of cost cluster, 583 (23%) with reduced costs, and 300 (12%) with increased costs if they had undergone video-assisted thoracoscopic surgery approach. The 5 overall highest cost predictors were patient admission from the clinic, diagnosis of metastatic cancer, presence of cancer, urgent hospital admission, and dementia. CONCLUSION: K-means cluster analysis and machine learning identify a patient population that may undergo video-assisted thoracoscopic surgery or robotic lobectomy without a significant difference in total cost. Local interpretable model-agnostic explanation identifies individual patient factors contributing to cost. Application of this modeling may reliably stratify high-cost patients into lower-cost approaches and provide a rationale for reducing expenditure.

Health care and socioeconomic costs for long-term survivors after implementation of checkpoint-inhibitors and targeted agents for metastatic melanoma.

BACKGROUND: Real-life data on health care costs and loss of productivity after implementing new agents for metastatic melanoma are important to supplement model-based economic data. MATERIALS AND METHODS: All patients registered in the Danish Metastatic Melanoma Database (DAMMED) and the National Patient Registry in 2007-2011 were compared to 2012-2016 after the implementation of checkpoint inhibitors and targeted therapy. Health care costs, social transfer income (STI), and loss of productivity were calculated with a 2-step one model generalised linear regression (GLM) model. Medicine costs were calculated separately. RESULTS: In 2007-2011, 70 (15%) out of 464 patients were long-term survivors compared to 347 (32%) out of 1089 patients in 2012-2016. Total health care costs per patient year were significantly lower in the first treatment year (€41.457 versus €60.547, relative change (RC) 0.72, 95% confidence interval (CI) 0.56-0.94, p = 0.015) and without significant difference the second year in 2012-2016 compared to 2007-2011. Medicine costs per patient year increased the first (€85.464 versus €26.339, RC 3.39, 95% CI 2.61-4.41, p < 0.001) and the second (€26.464 versus €11.150, RC 2.59, 95% CI 1.98-3.40, p < 0.001) year in 2012-2016 compared to 2007-2011. Productivity increased for long-term survivors in 2012-2016 in contrast to 2007-2011. CONCLUSION: Implementation of targeted therapy and checkpoint-inhibitors has increased medicine costs more than three-fold for long-term survivors. Total health care costs excluding medicine costs were significantly lower for long-term survivors the first and without change the second treatment year in 2012-2016 compared to 2007-2011. However, the number of treated patients increased which leads to an increase in overall total health care costs. Importantly, productivity increased for long-term survivors in 2012-2016.

Multimodal assessment after total neoadjuvant therapy versus standard neoadjuvant chemoradiotherapy in locally advanced rectal cancer accurately predicts complete responders.

PURPOSE: This study aimed to compare local regrowth rates after total neoadjuvant therapy (TNT) versus standard neoadjuvant chemoradiotherapy (SNCRT) in locally advanced rectal cancer (LARC) patients that were strictly selected and assessed with a multimodal approach. Secondary outcomes were 4-year disease-free (DFS) and overall survival (OS) rates. METHODS: Locally advanced rectal cancer patients without distant metastases treated at Koç Healthcare Group between January 2014 and January 2021 were included. Patients were assessed for complete response with a combination of digital rectal exam, endoscopy, and magnetic resonance imaging with a dedicated rectum protocol. The systemic evaluation was performed with an upper abdomen MRI using intravenous hepatobiliary contrast agent and a thorax CT. RESULTS: Of the 270 patients with LARC, 182 fulfilled the inclusion criteria. Ninety-seven (53.3%) underwent TNT, while 85 (46.7%) underwent SNCRT. A cumulative combination of pathological and sustained clinical complete response was significantly higher in the TNT group than in the SNCRT (45.4% vs. 20.0%, p < 0.0001). After a median follow-up of 48 months, seven patients in the W&W group had regrowth [TNT: 4 (10.8%) vs. SNCRT: 3 (23.1%), p = 0.357]. Based on pathological examination, complete/near complete mesorectum rates (p = 1.000) and circumferential resection margin positivity rates (p = 1.000) were similar between the groups. The 4-year DFS and OS rates were comparable. The patients with clinical or pathological complete response had significantly longer overall survival (p = 0.017) regardless of the type of neoadjuvant treatment. CONCLUSIONS: Multimodal assessment after TNT effectively detects complete responders, resulting in low local recurrence and increased cumulative complete response rates. However, these outcomes did not translate into a survival advantage.

Assessment of the level III of Inoue by preoperative endoscopic ultrasound and elastography: a novel approach to predict a periarterial divestment technique in borderline resectable (BR) or locally advanced (LA) pancreatic adenocarcinoma-How I do it.

BACKGROUND: Periarterial divestment is a surgical technique to approach borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) with arterial involvement. There are no reports in the literature regarding the role of endoscopic ultrasound and elastography (EUS-EG) in exploring the integrity of Inoue's level III and its correlation with the periarterial divestment technique feasibility. Our research is aimed at exploring the role of EUS-EG in this scenario. METHODS: We describe our approach to Inoue's level II by EUS-EG in patients with BR and LA pancreatic cancer patients after neoadjuvant chemotherapy. RESULTS: Between June 2019 and December 2020, four patients out of 25 were eligible to perform a preoperative EUS-EG. In all cases, Inoue's level III integrity was corroborated by EUS-EG and confirmed posteriorly in the surgical scenario where a periarterial divestment technique was feasible. Vein resections were necessary in all cases, with no need for arterial resection. An R0 (> 1 mm) margin was achieved in all patients, and the histopathological assessment showed the presence of neurovascular tissue at the peripheral arterial margin. CONCLUSION: Preoperatively, EUS-EG is a novel approach to explore the integrity of Inoue's level III and could be helpful to preclude a periarterial divestment technique in borderline resectable or locally advanced pancreatic adenocarcinoma with arterial involvement.

The First Population-Level Description of Women Diagnosed With Invasive Breast Cancer in Costa Rica From 2008 to 2012: A Cross-Sectional Study.

INTRODUCTION: Breast cancer is the leading cause of cancer-related deaths among women worldwide. In Costa Rica, it ranks first in incidence and fourth in terms of mortality. However, there is a lack of comprehensive information on treatment patterns and outcomes for breast cancer patients in Costa Rica. METHODS: This study utilized data from the National Tumor Registry, which was merged with the Costa Rica Social Security Fund (CCSS) to ensure comprehensive access to clinical information. The study is prospective and focused on patients diagnosed with breast cancer between January 2008 and December 2012. This combined dataset allowed for a more comprehensive analysis of patient characteristics, treatment patterns, and outcomes related to breast cancer in Costa Rica. RESULTS: Among the 4775 patients diagnosed during this period, 3160 met the inclusion criteria for our study. The average age at diagnosis was 59.1 years, with 32.5% of patients being over the age of 65. Most of the patients (55.4%) identified themselves as homemakers, while 46.5% underwent core needle biopsy for diagnosis. Approximately 60% of women were diagnosed with early-stage disease (IA, IIA, and IIB), while 1.7% had metastatic disease, mainly affecting the bone. The mean interval between diagnosis and surgery was 72 days. Most patients (88.7%) received surgery as their initial treatment, and over half (54.4%) received some form of adjuvant therapy. Additionally, 85.6% of patients completed their prescribed treatment. CONCLUSION: This study provides a comprehensive and detailed description of the characteristics and treatment patterns among breast cancer patients in Costa Rica. The findings contribute to our understanding of the disease in this population and can serve as a foundation for further research and improvement in breast cancer management and care.

Analysis of cost-effectiveness of chemotherapeutic agents and new therapies for the management of unresectable and metastatic melanoma.

BACKGROUND: The advent of targeted therapies and immunotherapies has revolutionized metastatic melanoma (MM) management but their use is associated with high daily costs compared to chemotherapies: €2 for dacarbazine versus €175 for immunotherapies and €413 for targeted therapies. While overall survival (OS) has increased, healthcare expenditures are expected to double by 2030. OBJECTIVES: The aim of this study was to estimate the median OS and costs for MM patients in order to evaluate the effectiveness of new biological or targeted therapies (NT) used since 2013 compared to chemotherapies. MATERIALS & METHODS: This was a retrospective monocentric cost-effectiveness analysis performed in CHU Nantes (Nantes University Hospital). All MM patients treated with conventional chemotherapy as first-line treatment between 2008 and 2012 were included (CHEMO group). The same number of patients treated with NT as first-line between 2013 and 2017 were included (NT group). RESULTS: In total, 161 patients were included in each group. The mean age at diagnosis was 64.7±2.4 years in the CHEMO group and 65.3±2.4 years in the NT group (not significant). The men/women ratio was 1.48 and 1.27, respectively, (not significant). The median OS was 158 days in the CHEMO group and 395 days in the NT group (p<0.001). Treatment cost was €10,280/patient versus €94,676/patient, respectively. The mean incremental cost-effectiveness ratio was €90,184/LY (95% CI: €59,637; €166,395). CONCLUSION: Our study assessed clinical and economic features associated with MM management before and after the advent of NT. Costs and life expectancy have increased. NT appears to be cost-effective.

A contemporary assessment of total neoadjuvant therapy (TNT) protocols for locally advanced rectal cancer: adoption and expert perspectives at German Cancer Society (DKG)-certified colorectal cancer centers.

PURPOSE: The treatment paradigm for locally advanced rectal cancer (LARC) is shifting toward the total neoadjuvant therapy (TNT) concept, which administered systemic chemotherapy in the neoadjuvant setting, either before or after chemoradiotherapy (CRT) or short-course radiotherapy (SCRT). First results have shown higher pathologic complete response (pCR) rates and a favorable impact on disease-free survival (DFS). Our study aimed to evaluate the current clinical practice and expert opinion regarding TNT for locally advanced rectal cancer across DKG (German Cancer Society)-certified colorectal cancer centers. METHODS: A comprehensive online questionnaire, constituted of 14 TNT-focused queries targeting patients with locally advanced rectal cancer, was conducted among DKG-certified colorectal cancer centers registered within the database of the Addz (Arbeitsgemeinschaft Deutscher Darmzentren) between December 2022 and January 2023. RESULTS: A significant majority (68%) indicated that they treated between 0 and 10 patients using a TNT protocol. Only a third (36%) of these centers participated in patient enrollment for a TNT study. Despite this, 84% of centers reported treating patients in a manner analogous to a TNT study, with the RAPIDO regimen being the most prevalent approach, employed by 60% of the respondents. The decision to adopt a TNT approach was primarily influenced by factors, such as the lower third of the rectum (93% of centers), cT4 stage (86% of centers), and a positive circumferential resection margin (80% of centers). Regarding concerns, 65% of the survey respondents expressed no reservations about the TNT concept, while 35% had concerns. In particular, there appears to be disagreement and uncertainty in regard to a clinical complete response and the "Watch and Wait" approach. While some centers adopt the watch-and-wait approach (42%), others only utilize it when extirpation is otherwise necessary (39%), and a portion still proceeds with surgery as initially planned (19%). The survey also addressed unmet needs, which were elaborated in the free-text responses. Overall, there was high interest in participating in planned observational studies. CONCLUSIONS: This study presents an overview of current clinical practice and unmet needs within DKG-certified German colorectal cancer centers. It is noteworthy that total neoadjuvant therapy (TNT) is predominantly performed outside of clinical trials. Moreover, across the centers, there is significant heterogeneity in handling clinical complete response and adopting the "watch and wait" approach. Further research is needed to establish standardization in the care of locally advanced rectal cancer.

Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors.

BACKGROUND: Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. PATIENTS AND METHODS: This retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. RESULTS: Among the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min-max: 7-173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27-0.58). CONCLUSION: Treatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.

Comparing Risk for Second Primary Cancers After Intensity-Modulated vs 3-Dimensional Conformal Radiation Therapy for Prostate Cancer, 2002-2015.

Importance: Compared with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) can spare nearby tissue but may result in increased scatter radiation to distant normal tissue, including red bone marrow. It is unclear whether second primary cancer risk varies by radiotherapy type. Objective: To evaluate whether radiotherapy type (IMRT vs 3DCRT) is associated with second primary cancer risk among older men treated for prostate cancer. Design, Setting, and Participants: In this retrospective cohort study of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries (2002-2015), male patients aged 66 to 84 diagnosed with a first primary nonmetastatic prostate cancer from 2002 to 2013, as reported to SEER, and who received radiotherapy (IMRT and/or 3DCRT without proton therapy) within the first year following prostate cancer were identified. The data were analyzed from January 2022 through June 2022. Exposure: Receipt of IMRT and 3DCRT, based on Medicare claims. Main Outcomes and Measures: The association between radiotherapy type and development of a subsequent hematologic cancer at least 2 years after prostate cancer diagnosis or a subsequent solid cancer at least 5 years after prostate cancer diagnosis. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional regression. Results: The study included 65 235 2-year first primary prostate cancer survivors (median [range] age, 72 [66-82] years; 82.2% White patients) and 45 811 5-year survivors with similar demographic characteristics (median [range] age, 72 [66-79] years; 82.4% White patients). Among 2-year prostate cancer survivors (median [range] follow-up, 4.6 [0.003-12.0] years), 1107 second hematologic cancers were diagnosed (IMRT, 603; 3DCRT, 504). Radiotherapy type was not associated with second hematologic cancers overall or any specific types evaluated. Among 5-year survivors (median [range] follow-up, 3.1 [0.003-9.0] years), 2688 men were diagnosed with a second primary solid cancer (IMRT, 1306; 3DCRT, 1382). The overall HR for IMRT vs 3DCRT was 0.91 (95% CI, 0.83-0.99). This inverse association was restricted to the earlier calendar year period of prostate cancer diagnosis (HR2002-2005 = 0.85; 95% CI, 0.76-0.94; HR2006-2010 = 1.14; 95% CI, 0.96-1.36), with a similar pattern observed for colon cancer (HR2002-2005 = 0.66; 95% CI, 0.46-0.94; HR2006-2010 = 1.06; 95% CI, 0.59-1.88). Conclusions and Relevance: The results of this large, population-based cohort study suggest that IMRT for prostate cancer is not associated with an increased risk of second primary cancers, either solid or hematologic, and any inverse associations may be associated with calendar year of treatment.

Cost-Effectiveness Analysis: Selective Use of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer.

BACKGROUND: Locally advanced rectal cancer has high cure rates with trimodal therapy. Studies sparing neoadjuvant chemoradiation in selected patients show comparable outcomes. OBJECTIVE: This study aimed to determine the cost-effectiveness of selective use of neoadjuvant chemoradiation in this population. DESIGN: A cost-effectiveness analysis model compared selective and blanket use chemoradiation for locally advanced rectal cancer. SETTINGS: Literature review, expert consensus, and a prospective database populated the model. Health care utilization costs were based on information from the Centers for Medicare and Medicaid Services. PATIENTS: Adult patients with stage II and III rectal cancer were selected. MAIN OUTCOMES MEASURES: Primary outcomes were cost, effectiveness in quality-adjusted disease-free life years, net monetary benefit, and incremental cost-effectiveness ratios in dollars per quality-adjusted disease-free life years. Base-case 5-year disease-free survival for both strategies was 65%. One-way sensitivity analysis found the probability of 5-year disease-free survival for selective ranged between 40% and 65%. Probabilistic sensitivity analysis assessed second-order variability. RESULTS: Base-case 5-year disease-free survival demonstrated selective use is dominant with lower cost and higher quality-adjusted disease-free life years. For selective use, cost is $153,176, effectiveness is 2.71 quality-adjusted life years, and net monetary benefit is -$17,564 and for blanket use cost is $176,362, effectiveness is 2.64 quality-adjusted life years, and net monetary benefit is -$44,217. One-way sensitivity analysis shows selective use is dominant for disease-free survival above 61.25% and is preferred for disease-free survival above 53.7%. Probabilistic sensitivity analysis shows selective use is optimal in 88% of the iterations for a population of 10,000 patients. LIMITATIONS: Model was based on data from the literature, prospective database, and expert consensus. CONCLUSION: In a population of patients with locally advanced rectal cancer with base-case disease-free survival of 65%, selective use of neoadjuvant chemoradiation is the superior strategy as long as disease-free survival in this group remains above 53%. See Video Abstract at http://links.lww.com/DCR/C199. ANLISIS DE COSTOEFECTIVIDAD USO SELECTIVO DE QUIMIORRADIACIN NEOADYUVANTE EN CNCER DE RECTO LOCALMENTE AVANZADO: ANTECEDENTES:El cáncer de recto localmente avanzado tiene altas tasas de curación con la terapia trimodal. Los estudios que evitan la quimiorradiación neoadyuvante en pacientes seleccionados muestran resultados comparables.OBJETIVO:Determinar la relación costo-efectividad del uso selectivo de quimiorradiación neoadyuvante en esta población.DISEÑO:Un modelo de análisis de costo-efectividad comparó la quimiorradiación selectiva y de uso general para el cáncer de recto localmente avanzado.AJUSTES:Revisión de literatura, consenso de expertos y una base de datos prospectiva poblaron el modelo. Los costos de utilización de la atención médica se basaron en los Centros de Servicios de Medicare y Medicaid.PACIENTES:Se seleccionaron pacientes adultos con cáncer de recto en estadio II y III.PRINCIPALES MEDIDAS DE RESULTADOS:Los resultados primarios fueron el costo, efectividad en años de vida sin enfermedad ajustados por calidad, el beneficio monetario neto y la relación costo-efectividad incremental en $/años de vida sin enfermedad ajustados por calidad. La supervivencia libre de enfermedad a 5 años del caso base para ambas estrategias fue del 65%. El análisis de sensibilidad unidireccional varió la probabilidad de supervivencia libre de enfermedad a 5 años para uso selectivo entre 40%-65%. El análisis de sensibilidad probabilístico evaluó la variabilidad de segundo orden.RESULTADOS:El caso base de 5 años de supervivencia libre de enfermedad demostró que el uso selectivo es dominante con menor costo y años de vida libre de enfermedad ajustados de mayor calidad. El costo, la efectividad y el beneficio monetario neto para el uso selectivo y general fueron ($153 176; 2,71 QALY; -$17 564) y ($176 362; 2,64 QALY; -$44 217). El análisis de sensibilidad unidireccional demostró que el uso selectivo es dominante para la supervivencia sin enfermedad por encima del 61,25% y se prefiere para la supervivencia sin enfermedad por encima del 53,7%. El análisis de sensibilidad probabilístico demostró que el uso selectivo es óptimo en el 88% de las iteraciones para una población de 10 000 pacientes.LIMITACIONES:Modelo basado en datos de literatura, base de datos prospectiva y consenso de expertos.CONCLUSIÓN:En una población de pacientes con cáncer de recto localmente avanzado con caso base de supervivencia libre de enfermedad del 65%, el uso selectivo de quimiorradiación neoadyuvante para el cáncer de recto localmente avanzado es la estrategia superior, siempre y cuando la supervivencia libre de enfermedad en este grupo se mantenga por encima del 53%. Consulte Video Resumen en http://links.lww.com/DCR/C199. (Traducción-Dr. Fidel Ruiz Healy).

Short-Term Outcomes and Cost-Effectiveness between Long-Course Chemoradiation and Short-Course Radiotherapy for Locally Advanced Rectal Cancer.

PURPOSE: Long-course chemoradiotherapy (LCRT) has been widely recommended in a majority of rectal cancer patients. Recently, encouraging data on short-course radiotherapy (SCRT) for rectal cancer has emerged. In this study, we aimed to compare these two methods in terms of short-term outcomes and cost analysis under the Korean medical insurance system. MATERIALS AND METHODS: Sixty-two patients with high-risk rectal cancer, who underwent either SCRT or LCRT followed by total mesorectal excision (TME), were classified into two groups. Twenty-seven patients received 5 Gy×5 with two cycles of XELOX (capecitabine 1000 mg/m² and oxaliplatin 130 mg/m² every 3 weeks) followed by TME (SCRT group). Thirty-five patients received capecitabine-based LCRT followed by TME (LCRT group). Short-term outcomes and cost estimation were assessed between the two groups. RESULTS: Pathological complete response was achieved in 18.5% and 5.7% of patients in the SCRT and LCRT groups, respectively (p=0.223). The 2-year recurrence-free survival rate did not show significant difference between the two groups (SCRT vs. LCRT: 91.9% vs. 76.2%, p=0.394). The average total cost per patient for SCRT was 18% lower for inpatient treatment (SCRT vs. LCRT: $18787 vs. $22203, p<0.001) and 40% lower for outpatient treatment (SCRT vs. LCRT: $11955 vs. $19641, p<0.001) compared to LCRT. SCRT was shown to be the dominant treatment option with fewer recurrences and fewer complications at a lower cost. CONCLUSION: SCRT was well-tolerated and achieved favorable short-term outcomes. In addition, SCRT showed significant reduction in the total cost of care and distinguished cost-effectiveness compared to LCRT.

A UK cost-effectiveness analysis of trifluridine/tipiracil for heavily pretreated metastatic gastroesophageal cancers.

Background: The current work was designed to estimate the cost-effectiveness of trifluridine/tipiracil (T/T) versus best supportive care (BSC) for patients with advanced stage or metastatic gastroesophageal cancer (mGC) from a UK perspective. Materials & methods: A partitioned survival analysis was undertaken using data from the phase III TAGS trial. A jointly fitted lognormal model was selected for overall survival and individual generalized gamma models were chosen for progression-free survival and time-to-treatment-discontinuation. The primary outcome was the cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were undertaken to investigate uncertainty. Results: Compared with BSC, T/T was associated with a cost per QALY gained of £37,907. Conclusion: T/T provides a cost-effective treatment option for mGC in the UK setting.

Selection Bias in Real-World Data Studies Used to Support Health Technology Assessments: A Case Study in Metastatic Cancer.

Real-world evidence has been increasingly used to support evaluations of emerging therapies. These investigations are often conducted in settings that may not be representative of the underlying population. The purpose of this investigation was to empirically quantify the magnitude of this selection bias. Individuals diagnosed with solid metastatic cancer in Alberta, Canada, between 2010-2019 were identified using the provincial cancer registry for 13 common metastatic sites. Two outcomes used to support oncology reimbursement decisions were examined: the proportion of individuals who initiated systemic therapy and median overall survival (OS). These outcomes were assessed in the entire population and in a subset of individuals who were referred to a medical oncologist. Among the 23,152 individuals in the entire population, 40.8% (95% CI: 40.2-41.4) initiated systemic therapy, and the median OS from diagnosis was 5.4 months (95% CI: 5.3-5.6). Among those who were referred to a medical oncologist (n = 13,372; 57.8%), 67.4% (95% CI: 66.6-68.2) initiated systemic therapy, and the median OS from diagnosis was 11.2 months (95% CI: 10.9-11.5). The magnitude of bias varied by cancer site where lower referral rates were associated with greater bias. Non-referral is an important source of selection bias in real-world investigations. Studies that rely on limited-catchment real-world data should be interpreted with caution, particularly in metastatic cancer settings.