Preoperative chemoradiotherapy in older patients with rectal cancer guided by comprehensive geriatric assessment within a multidisciplinary team-a multicenter phase II trial.

BACKGROUND: The purpose of this study was to evaluate the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for locally advanced rectal cancer in older people who were classified as "fit" by comprehensive geriatric assessment (CGA). METHODS: A single-arm, multicenter, phase II trial was designed. Patients were eligible for this study if they were aged 70 years or above and met the standards of "fit" (SIOG1) as evaluated by CGA and of the locally advanced risk category. The primary endpoint was 2-year disease-free survival (DFS). Patients were scheduled to receive preCRT (50 Gy) with raltitrexed (3 mg/m2 on days 1 and 22). RESULTS: One hundred and nine patients were evaluated by CGA, of whom eighty-six, eleven and twelve were classified into the fit, intermediate and frail category. Sixty-eight fit patients with a median age of 74 years were enrolled. Sixty-four patients (94.1%) finished radiotherapy without dose reduction. Fifty-four (79.3%) patients finished the prescribed raltitrexed therapy as planned. Serious toxicity (grade 3 or above) was observed in twenty-four patients (35.3%), and fourteen patients (20.6%) experienced non-hematological side effects. Within a median follow-up time of 36.0 months (range: 5.9-63.1 months), the 2-year overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) rates were 89.6% (95% CI: 82.3-96.9), 92.4% (95% CI: 85.9-98.9) and 75.6% (95% CI: 65.2-86.0), respectively. Forty-eight patients (70.6%) underwent surgery (R0 resection 95.8%, R1 resection 4.2%), the corresponding R0 resection rate among the patients with positive mesorectal fascia status was 76.6% (36/47). CONCLUSION: This phase II trial suggests that preCRT is efficient with tolerable toxicities in older rectal cancer patients who were evaluated as fit based on CGA. TRIAL REGISTRATION: The registration number on ClinicalTrials.gov was NCT02992886 (14/12/2016).

Disparities in mortality risk after diagnosis of hematological malignancies in 185 countries: A global data analysis.

This study was to report proxy measures for mortality risk in patients with hematological malignancies across 185 countries globally and explore its association with their socioeconomic status and treatment. The incidence, mortality, and 5-year prevalence data were extracted from the GLOBOCAN database. The data regarding the human development index (HDI), gross national income (GNI), vulnerability index, and concordance with cancer Essential Medicines List (EML) were obtained from open-source reports. The ratio of mortality to 5-year-prevalence (MPR) and that of mortality to incidence (MIR) were calculated and age-standardized using Segi's world standard population. Finally, the possible associations were assessed using Pearson correlation analyses. In 2020, the global incidence, mortality, and 5-year prevalence of HMs were 1,278,362, 711,840, and 3,616,685, respectively. Global age-standardized MPR and MIR were 0.15 and 0.44, respectively; they varied significantly among 6 regions, 185 countries, 4 HM types, and 4 HDI groups worldwide. Older populations always had higher ratios. The correlation of MPRs and MIRs with HDI, GNI, and concordance with cancer EML was negative, whereas it was positive with the vulnerability index (lower was better). Increasing access to cancer drugs in resource-limited regions with a focus on vulnerable children may aid in reducing HM-related mortality risk.

Assessment of delivered dose in prostate cancer patients treated with ultra-hypofractionated radiotherapy on 1.5-Tesla MR-Linac.

Objective: To quantitatively characterize the dosimetric effects of long on-couch time in prostate cancer patients treated with adaptive ultra-hypofractionated radiotherapy (UHF-RT) on 1.5-Tesla magnetic resonance (MR)-linac. Materials and methods: Seventeen patients consecutively treated with UHF-RT on a 1.5-T MR-linac were recruited. A 36.25 Gy dose in five fractions was delivered every other day with a boost of 40 Gy to the whole prostate. We collected data for the following stages: pre-MR, position verification-MR (PV-MR) in the Adapt-To-Shape (ATS) workflow, and 3D-MR during the beam-on phase (Bn-MR) and at the end of RT (post-MR). The target and organ-at-risk contours in the PV-MR, Bn-MR, and post-MR stages were projected from the pre-MR data by deformable image registration and manually adapted by the physician, followed by dose recalculation for the ATS plan. Results: Overall, 290 MR scans were collected (85 pre-MR, 85 PV-MR, 49 Bn-MR and 71 post-MR scans). With a median on-couch time of 49 minutes, the mean planning target volume (PTV)-V95% of all scans was 97.83 ± 0.13%. The corresponding mean clinical target volume (CTV)-V100% was 99.93 ± 0.30%, 99.32 ± 1.20%, 98.59 ± 1.84%, and 98.69 ± 1.85%. With excellent prostate-V100% dose coverage, the main reason for lower CTV-V100% was slight underdosing of seminal vesicles (SVs). The median V29 Gy change in the rectal wall was -1% (-20%-17%). The V29 Gy of the rectal wall increased by >15% was observed in one scan. A slight increase in the high dose of bladder wall was noted due to gradual bladder growth during the workflow. Conclusions: This 3D-MR-based dosimetry analysis demonstrated clinically acceptable estimated dose coverage of target volumes during the beam-on period with adaptive ATS workflow on 1.5-T MR-linac, albeit with a relatively long on-couch time. The 3-mm CTV-PTV margin was adequate for prostate irradiation but occasionally insufficient for SVs. More attention should be paid to restricting high-dose RT to the rectal wall when optimizing the ATS plan.

Cost-effectiveness of postmastectomy hypofractionated radiation therapy vs conventional fractionated radiation therapy for high-risk breast cancer.

BACKGROUND: The phase 3 NCT00793962 trial demonstrated that postmastectomy hypofractionated radiation therapy (HFRT) was noninferior to conventional fractionated radiation therapy (CFRT) in patients with high-risk breast cancer. This study assessed the cost-effectiveness of postmastectomy HFRT vs CFRT based on the NCT00793962 trial. METHODS: A Markov model was adopted to synthesize the medical costs and health benefits of patients with high-risk breast cancer based on data from the NCT00793962 trial. Main outcomes were discounted lifetime costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). We employed a time-dependent horizon from Chinese, French and USA payer perspectives. Model robustness was evaluated with one-way and probabilistic sensitivity analyses. RESULTS: Patients receiving CFRT versus HFRT gained an incremental 0.0163 QALYs, 0.0118 QALYs and 0.0028 QALYs; meanwhile an incremental cost of $2351.92, $4978.34 and $8812.70 from Chinese, French and USA payer perspectives, respectively. Thus CFRT versus HFRT yielded an ICER of $144,281.47, $420,636.10 and $3,187,955.76 per QALY from Chinese, French and USA payer perspectives, respectively. HFRT could maintain a trend of >50% probabilities of cost-effectiveness below a willingness-to-pay (WTP) of $178,882.00 in China, while HFRT was dominant relative to CFRT, regardless of the WTP values in France and the USA. Sensitivity analyses indicated that the ICERs were most sensitive to the parameters of overall survival after radiotherapy. CONCLUSIONS: Postmastectomy HFRT could be used as a cost-effective substitute for CFRT in patients with high-risk breast cancer and should be considered in appropriately selected patients.

Safety and efficacy of preoperative chemoradiotherapy in fit older patients with intermediate or locally advanced rectal cancer evaluated by comprehensive geriatric assessment: A planned interim analysis of a multicenter, phase II trial.

BACKGROUND AND PURPOSE: Comprehensive geriatric assessment (CGA) is a diagnostic method to assess the physical and mental health status of older patients. The purpose of this study was to assess the safety and efficacy of preoperative concurrent chemoradiotherapy (preCRT) for intermediate or locally advanced rectal cancer in older people who were classified as "fit" by CGA. The interim analysis focusing on safety was reported here as the first part of this trial. METHODS AND MATERIALS: This is a single arm, multicenter, phase II trial. The eligible patients for this study were aged 70 years or above that fulfilled the standard of intermediate or locally advanced risk category, and met the standard of fit (SIOG1) evaluated by CGA. All patients received preCRT (50 Gy) with Raltitrexed (3 mg/m2 on d1 and d22). Qualitative and quantitative variables were described using descriptive statistics. The surgery adherence predicting was analyzed by multivariate logistic regression. RESULTS: Thirty-nine fit patients were enrolled. All patients except one finished radiotherapy without dose reduction. Thirty-two patients finished the prescribed Raltitrexed therapy as scheduled. A serious toxicity was observed in 12 patients (30.8%), and only six patients (15.4%) experienced non-hematological side effects. CONCLUSION: Overall, our results showed that preCRT was feasible and safe in older patients with rectal cancer who were evaluated as fit based on CGA, supporting the use of CGA to tailor oncological treatment and predict the tolerance of a specific therapy. Completing this trial as planned would provide further valuable insights.

Postmastectomy chest wall radiotherapy with single low-energy electron beam: An assessment of outcome and prognostic factors.

PURPOSE: This study aimed to evaluate the outcome of patients who had received postmastectomy chest wall radiotherapy using a single electron beam, and to identify the relevant factors that influenced prognosis. METHODS: The medical records of patients with breast cancer treated with postmastectomy radiotherapy from January 2000 to December 2004 were retrospectively analyzed (n = 328). Two hundred seventy-one (82.6%) patients were staged as (tumor-nodes-metastasis [TNM]) T3-4, any N, M0; or T1-2, N2-3, M0, and 57 (17.4%) patients were staged as T1-2, N1, M0. All patients received chest wall radiation with a 6-10 MeV electron beam. In addition, 327 patients (99.7%) received supraclavicular node radiation, 67 (20.4%) axillary radiation, and 35 (10.7%) internal mammary chain (IMC) radiation. Chemotherapy with anthracycline and taxane was given to 323 patients (98.5%). Of patients with positive hormone receptor, 183 (82.8%) received hormone therapy and 8 patients with negative and 3 patients with unknown hormone receptor received hormone therapy. Locoregional recurrence (LRR), distant metastasis (DM), and overall survival (OS) were calculated using the Kaplan-Meier method, and the differences assessed by log-rank test. RESULTS: The median follow-up time was 78 months (range, 5-123 months) for patients who remained alive. The 5-year LRR, DM, disease-free survival and OS rates were 5.9%, 26.2%, 72.5%, and 83.1%, respectively. LRR occurred in 1 or more sites in 21 patients. The 5-year recurrence rates in the chest wall, supraclavicular node, axilla, and internal mammary chain were 1.9%, 2.3%, 2.9%, and 0%, respectively. In multivariate analysis, hormone therapy was the only independent favorable prognostic factor for LRR (P = .017). LRR was significantly associated with DM and OS. The 5-year DM rate was 82.9% and 22.7% (P < .0001) and the 5-year OS rate was 52.8% and 84.7% (P < .0001) for patients with or without LRR. The treatment-related toxicity was low, with the incidence of symptomatic pneumonitis being 0.3%. CONCLUSIONS: Breast cancer patients can be treated with postmastectomy single electron beam radiotherapy with excellent local control and low toxicity.