Optimizing Clinical Implementation of Hypofractionation: Comprehensive Evidence Synthesis and Practical Guidelines for Low- and Middle-Income Settings.

The global cancer burden, especially in low- and middle-income countries (LMICs), worsens existing disparities, amplified by the rising costs of advanced treatments. The shortage of radiation therapy (RT) services is a significant issue in LMICs. Extended conventional treatment regimens pose significant challenges, especially in resource-limited settings. Hypofractionated radiotherapy (HRT) and ultra-hypofractionated/stereotactic body radiation therapy (SBRT) offer promising alternatives by shortening treatment durations. This approach optimizes the utilization of radiotherapy machines, making them more effective in meeting the growing demand for cancer care. Adopting HRT/SBRT holds significant potential, especially in LMICs. This review provides the latest clinical evidence and guideline recommendations for the application of HRT/SBRT in the treatment of breast, prostate, and lung cancers. It emphasizes the critical importance of rigorous training, technology, stringent quality assurance, and safety protocols to ensure precise and secure treatments. Additionally, it addresses practical considerations for implementing these treatments in LMICs, highlighting the need for comprehensive support and collaboration to enhance patient access to advanced cancer care.

Lessons learned for spine SABR?

•SABR has shown survival benefits in oligometastatic cases, particularly in low-volume metastatic disease states.•Spine SABR offers potential improvements in local control, and pain response for metastatic spine tumors.•Technical requirements for SABR, like advanced image guidance and immobilization systems, are increasingly available.•Current data suggests high local control rates (75-95%) and variable pain responses (40-90%) with SABR using single or multi-fraction regimens.•Further randomized trials are needed to explore SABR applications in different scenarios and populations, while considering global health aspects for wider accessibility.

Analysis of multicatheter interstitial brachytherapy: Accelerated partial breast irradiation in a retrospective cohort of early-stage breast cancer patients.

PURPOSE: To determine cardiac dose received by patients treated with high dose rate interstitial brachytherapy. Patients with early-stage, node negative breast cancer can be treated using multi-catheter interstitial brachytherapy accelerated partial breast irradiation (MIB-APBI), with the benefit of reduced treatment volumes and favorable toxicity. METHODS AND MATERIALS: We conducted a retrospective review of left-sided breast cancer patients treated using MIB-APBI at our institution since 2014. The mean heart dose (MHD) was calculated using the Oncentra 3.2 planning system. The minimum distance between the planning target volume (PTVeval) and heart contour was measured manually. FINDINGS: 81 patients were included. The upper outer quadrant was the most common site. The MHD was 97.8 cGy (EQD2a/b=2) (range 22-229 cGy). MHD significantly correlated with the closest distance between PTVeval and heart contour (correlation coefficient -0.823, p <0.001); size of PTVeval (cc) and quadrant location did not. CONCLUSIONS: Appropriately selected women with early-stage, low-risk, left-sided breast cancer who received MIB-APBI had acceptable MHD. There was a strong correlation between the distance of PTVeval and MHD. Quadrant breast tumor is in cannot be used as a surrogate for MHD in brachytherapy. Our findings contribute to the growing evidence of the utility and safety of MIB-APBI.

Survival outcomes and predicting intracranial metastasis in stage III non-small cell lung cancer treated with definitive chemoradiation: Real-world data from a tertiary cancer center.

PURPOSE/OBJECTIVE: Around 30% of patients with non-small cell lung cancers (NSCLC) are diagnosed with stage III disease at presentation, of which about 50% are treated with definitive chemoradiation (CRT). Around 65-80% of patients will eventually develop intracranial metastases (IM), though associated risk factors are not clearly described. We report survival outcomes and risk factors for development of IM in a cohort of patients with stage III NSCLC treated with CRT at a tertiary cancer center. MATERIALS/METHODS: We identified 195 patients with stage III NSCLC treated with CRT from January 2010 to May 2021. Multivariable logistic regression was used to generate odds ratios for covariates associated with development of IM. Kaplan-Meier analysis with the Log Rank test was used for unadjusted time-to-event analyses. P-value for statistical significance was set at < 0.05 with a two-sided test. RESULTS: Out of 195 patients, 108 (55.4%) had stage IIIA disease and 103 (52.8%) had adenocarcinoma histology. The median age and follow-up (in months) was 67 (IQR 60-74) and 21 (IQR 12-43), respectively. The dose of radiation was 60 Gy in 30 fractions for148 patients (75.9%). Of the 77 patients who received treatment since immunotherapy was available and standard at our cancer center, 45 (58.4%) received at least one cycle. During follow-up, 84 patients (43.1%) developed any metastasis, and 33 (16.9%) developed IM (either alone or with extracranial metastasis). 150 patients (76.9%) experienced a treatment delay (interval between diagnosis and treatment > 4 weeks). Factors associated with developing any metastasis included higher overall stage at diagnosis (p = 0.013) and higher prescribed dose (p = 0.022). Factors associated with developing IM included higher ratio of involved over sampled lymph nodes (p = 0.001) and receipt of pre-CRT systemic or radiotherapy for any reason (p = 0.034). On multivariate logistical regression, treatment delay (OR 3.9, p = 0.036) and overall stage at diagnosis (IIIA vs. IIIB/IIIC) (OR 2.8, p = 0.02) predicted development of IM. These findings were sustained on sensitivity analysis using different delay intervals. Median OS was not reached for the overall cohort, and was 43.1 months for patients with IM and 40.3 months in those with extracranial-only metastasis (p = 0.968). In patients with any metastasis, median OS was longer (p = 0.003) for those who experienced a treatment delay (48.4 months) compared to those that did not (12.2 months), likely due to expedited diagnosis and treatment in patients with a higher symptom burden secondary to more advanced disease. CONCLUSIONS: In patients with stage III NSCLC treated with definitive CRT, the risk of IM appears to increase with overall stage at diagnosis and, importantly, may be associated with experiencing a treatment delay (> 4 weeks). Metastatic disease of any kind remains the primary life-limiting prognostic factor in these patients with advanced lung cancer. In patients with metastatic disease, treatment delay was associated with better survival. Patients who experience a treatment delay and those initially diagnosed at a more advanced overall stage may warrant more frequent surveillance for early diagnosis and treatment of IM. Healthcare system stakeholders should strive to mitigate treatment delay in patients with locally NSCLC to reduce the risk of IM. Further research is needed to better understand factors associated with survival, treatment delay, and the development of IM after CRT in the immunotherapy era.

A Precise Approach for Radiotherapy of Breast Cancer.

Radiotherapy is an integral part of the multidisciplinary management of breast cancer (BC). There have been multiple recent advances in the delivery of radiotherapy, reviewed with a critical discussion of the evidence from trials investigating adjuvant ultra-hypofractionation and partial breast irradiation for early-stage BC, and the locoregional management of lymph nodes in locally advanced BC. Multiple precision medicine-based approaches have been developed as prognostic and/or predictive for BC patients and identifying biomarkers of radioresistance could help identify patients that may benefit from dose-escalated radiotherapy or radiosensitizers. Radiotherapy after breast reconstruction is an area of current controversy in the field, and we evaluated the decision-making considerations in this situation. The oligometastatic state is an emerging field for many cancer sites based on recent trials investigating ablative radiotherapy for oligometastatic BC. This chapter is an overview of radiotherapy for BC, with a focus on recent advances in early-stage, locally advanced, and oligometastatic disease.

Mortality due to cancer treatment delay: systematic review and meta-analysis.

OBJECTIVE: To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Published studies in Medline from 1 January 2000 to 10 April 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models. RESULTS: The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings. CONCLUSIONS: Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.

De-indexed estimated glomerular filtration rates: A simple step towards improving accuracy of drug dosing of renally excreted medications in moderate to severe obesity.

Kidney function is underestimated in obese individuals when standard equations are applied. Laboratory-reported estimated glomerular filtration rates (eGFR) report glomerular filtration rates corrected for body surface area in mL/min per 1.73 m2 using modification of diet in renal disease or the chronic kidney disease-Epidemiology Collaboration equations. This may result in premature discontinuation or reduction in dosage of renally excreted medications. Currently, there are no clinical guidelines defining thresholds beyond which physicians should consider de-indexing patient eGFR values. We compared standard and de-indexed eGFR values for 281 consecutive patients seen in our chronic kidney disease clinic. In our study, half of the patients with a body mass index above 35 had clinically significant changes in their eGFR, with an improvement in chronic kidney disease stage, when eGFR was de-indexed. We propose that eGFR de-indexing should be considered in patients with moderate to severe obesity when calculating the dose, especially for medications that are excreted by the kidneys.

The Oncotype Dx Assay in ER-Positive, HER2-Negative Breast Cancer Patients: A Real Life Experience from a Single Cancer Center.

OBJECTIVE: To determine the influence of the Oncotype Dx assay on the treatment of patients with Estrogen Receptor (ER)-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative, axillary lymph node-negative or micrometastatic carcinoma of the breast in a single cancer center. In addition, patients with intermediate Oncotype Dx recurrence scores were analyzed to assess the factors influencing therapeutic decisions for adjuvant chemotherapy. MATERIALS AND METHODS: Data from medical records of women diagnosed with carcinoma of the breast and qualified for the Oncotype Dx assay were extracted (OncoDx cohort). Patient demographic and cancer characteristics, genomic report, and course of treatment data, including survival outcomes and treatment decision-making, were analyzed. A matched cohort of patients with similar tumor stage and biology (ER-positive, HER2-negative) from the era before the introduction of the Oncotype Dx assay was analyzed for comparison (pre-OncoDx cohort). RESULTS: Two hundred and one patients were included in the OncoDx cohort and one hundred and sixty patients were included in the pre-OncoDx cohort. Oncotype Dx recurrence score (RS) was low (<11) in fifty-six patients (28%), intermediate (11-25) in one hundred and twenty-three patients (61.5%) and high (>25) in twenty one patients (10.5%). Demographic and cancer clinicopathologic characteristics between OncoDx and pre-OncoDx cohorts were similar. Overall, 10.9% of the patients in the OncoDx cohort received adjuvant chemotherapy, versus 23.8% of the patients in the pre-OncoDx cohort (Fisher exact p=0.003). Fewer patients were recommended adjuvant chemotherapy in the OncoDx era compared to the pre-OncoDx era (17.9% vs 30.6%, respectively, Fisher exact p=0.006). The decision to recommend chemotherapy within the intermediate-risk cohort was influenced by the patient's RS. The mean RS of patients in the intermediate-risk cohort who did not receive chemotherapy was 21.5 while the score of those that received chemotherapy was 24.6 (p=0.000). The series confirmed excellent PFS and OS for both OncoDx and pre-OncoDx cohorts. CONCLUSION: This single cancer center analysis confirms the avoidance of chemotherapy in the great majority of patients with early ER-positive, HER2-negative, lymph node-negative or micrometastatic carcinoma of the breast since the introduction of the Oncotype Dx assay. A higher recurrence risk score within the intermediate group may influence the decision for chemotherapy inclusion in the adjuvant treatment plan. A lower PR percentage by IHC and higher grade may predict higher Oncotype Dx scores.

Characterization of the Hot Anode Paste Compaction Process: A Computational and Experimental Study.

The aim of this work is to model and characterize green anode paste compaction behavior. For this purpose, a nonlinear viscoplastic constitutive law for compressible materials, based on the finite strain theory and the thermodynamic framework, was used. An experimental study was carried out to characterize axial and radial behaviors of the anode paste. To this end, simple compaction tests using a thin steel instrumented mold were performed at a temperature of 150 °C. Results of these experiments brought out the nonlinear mechanical behavior of the anode paste. Furthermore, they showed the importance of its radial behavior. The constitutive law was implemented in Abaqus software through the user's material subroutine VUMAT for explicit dynamic analysis. An inverse analysis procedure for material parameters identification showed that the model predicts compaction tests results with a good agreement. In order to assess the constitutive law predictive potential in situations involving density gradients, compaction tests using complex geometries such as slots and stub holes were carried out. Finite element simulation results showed the ability of the model to successfully predict density profiles measured by the X-ray tomography.

Prediction of Oncotype Dx recurrence score using clinical parameters: A comparison of available tools and a simple predictor based on grade and progesterone receptor.

OBJECTIVE/BACKGROUND: The Oncotype Dx test is a genomic test currently used in clinical practice to predict the risk of disease recurrence in estrogen receptor (ER)-positive, HER2-negative breast cancer patients with axillary lymph node-negative or micrometastatic disease. The test is one of several similar genomically based tests available. Although it has a good predictive value, it is expensive and thus constitutes a significant financial burden for health systems. Thus, several attempts have been made to devise low-cost tools that could predict the recurrence score derived from the genomic evaluation using easily obtainable clinical parameters. METHODS: Two previously proposed predictive tools were evaluated in a cohort of 201 patients that had undergone the Oncotype Dx test for their efficacy in predicting the Oncotype Dx Recurrence Score (RS). A simple predictor, named GR-PR, based on two available pathologic parameters, grade and progesterone receptor status was devised and also evaluated. RESULTS: The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of all three tools were compared and found to be similar for all cutoff points of Oncotype Dx RS. The accuracy of GR-PR was comparable to the best performing of the two other prediction tools for all four cutoff points. CONCLUSION: The simple GR-PR predictor proposed in this study seems to be at least as accurate as more complex tools and should be the preferred tool for the prediction of Oncotype Dx RS from clinicopathologic parameters when the Oncotype Dx test is not available.

FOLFIRINOX Chemotherapy in Metastatic Pancreatic Cancer: A Systematic Review and Meta-Analysis of Retrospective and Phase II Studies.

The introduction of the FOLFIRINOX regimen within the last decade marked the first progress in the clinical field of metastatic pancreatic cancer which had not seen any improvements in treatment availability for several years. In a phase III randomized clinical trial, FOLFIRINOX showed superior efficacy compared to the previous standard treatment of gemcitabine monotherapy. Nevertheless, it is unknown whether the superior results observed in this single phase III clinical trial can be translated more broadly to clinical practice. Our investigation sought to analyze all published evidence of the FOLFIRINOX regimen in series and phase II trials and compare it to the experience of the phase III study. Survival analysis revealed that FOLFIRINOX was associated with an Overall Survival of 10-11 months both in the trials and in off-trial settings, with response rates also similar in both settings. The adverse effect profile was consistent between the pooled phase II and off-trial experience and the FOLFIRINOX regimen arm observed in the randomized phase III trial.