Is prone free breathing better than supine deep inspiration breath-hold for left whole-breast radiotherapy? A dosimetric analysis.

PURPOSE: The advantage of prone setup compared with supine for left-breast radiotherapy is controversial. We evaluate the dosimetric gain of prone setup and aim to identify predictors of the gain. METHODS: Left-sided breast cancer patients who had dual computed tomography (CT) planning in prone free breathing (FB) and supine deep inspiration breath-hold (DiBH) were retrospectively identified. Radiation doses to heart, lungs, breasts, and tumor bed were evaluated using the recently developed mean absolute dose deviation (MADD). MADD measures how widely the dose delivered to a structure deviates from a reference dose specified for the structure. A penalty score was computed for every treatment plan as a weighted sum of the MADDs normalized to the breast prescribed dose. Changes in penalty scores when switching from supine to prone were assessed by paired t-tests and by the number of patients with a reduction of the penalty score (i.e., gain). Robust linear regression and fractional polynomials were used to correlate patients' characteristics and their respective penalty scores. RESULTS: Among 116 patients identified with dual CT planning, the prone setup, compared with supine, was associated with a dosimetric gain in 72 (62.1%, 95% CI: 52.6-70.9%). The most significant predictors of a gain with the prone setup were the breast depth prone/supine ratio (>1.6), breast depth difference (>31 mm), prone breast depth (>77 mm), and breast volume (>282 mL). CONCLUSION: Prone compared with supine DiBH was associated with a dosimetric gain in 62.1% of our left-sided breast cancer patients. High pendulousness and moderately large breast predicted for the gain.

Cardiopulmonary-related patient-reported outcomes in a randomized clinical trial of radiation therapy for breast cancer.

BACKGROUND: Long-term prospective patient-reported outcomes (PRO) after breast cancer adjuvant radiotherapy is scarce. TomoBreast compared conventional radiotherapy (CR) with tomotherapy (TT), on the hypothesis that TT might reduce lung-heart toxicity. METHODS: Among 123 women consenting to participate, 64 were randomized to CR, 59 to TT. CR delivered 50 Gy in 25 fractions/5 weeks to breast/chest wall and regional nodes if node-positive, with a sequential boost (16 Gy/8 fractions/1.6 weeks) after lumpectomy. TT delivered 42 Gy/15 fractions/3 weeks to breast/chest wall and regional nodes if node-positive, 51 Gy simultaneous-integrated-boost in patients with lumpectomy. PRO were assessed using the European Organization for Research and Treatment of Cancer questionnaire QLQ-C30. PRO scores were converted into a symptom-free scale, 100 indicating a fully symptom-free score, 0 indicating total loss of freedom from symptom. Changes of PRO over time were analyzed using the linear mixed-effect model. Survival analysis computed time to > 10% PRO-deterioration. A post-hoc cardiorespiratory outcome was defined as deterioration in any of dyspnea, fatigue, physical functioning, or pain. RESULTS: At 10.4 years median follow-up, patients returned on average 9 questionnaires/patient, providing a total of 1139 PRO records. Item completeness was 96.6%. Missingness did not differ between the randomization arms. The PRO at baseline were below the nominal 100% symptom-free score, notably the mean fatigue-free score was 64.8% vs. 69.6%, pain-free was 75.4% vs. 75.3%, and dyspnea-free was 84.8% vs. 88.5%, in the TT vs. CR arm, respectively, although the differences were not significant. By mixed-effect modeling on early ≤2 years assessment, all three scores deteriorated, significantly for fatigue, P ≤ 0.01, without effect of randomization arm. By modeling on late assessment beyond 2 years, TT versus CR was not significantly associated with changes of fatigue-free or pain-free scores but was associated with a significant 8.9% improvement of freedom from dyspnea, P = 0.035. By survival analysis of the time to PRO deterioration, TT improved 10-year survival free of cardiorespiratory deterioration from 66.9% with CR to 84.5% with TT, P = 0.029. CONCLUSION: Modern radiation therapy can significantly improve long-term PRO. TRIAL REGISTRATION: Trial registration number ClinicalTrials.gov NCT00459628 , April 12, 2007 prospectively.

Immunotherapy and Radiotherapy for Older Cancer Patients during the COVID-19 Era: Proposed Paradigm by the International Geriatric Radiotherapy Group.

BACKGROUND: Older cancer patients with locally advanced or metastatic disease may benefit from chemotherapy alone or combined with radiotherapy. However, chemotherapy is often omitted either because of physician bias or because of its underlying comorbidity, thus compromising their survival. The coronavirus disease 19 (COVID-19) pandemic is compounding this issue because of the fear of immunosuppression induced by chemotherapy on the elderly which makes them more vulnerable to the virus. SUMMARY: Immunotherapy has less effect on the patient bone marrow compared to chemotherapy. The potential synergy between radiotherapy and immunotherapy may improve local control and survival for older patients with selected cancer. Preliminary data are encouraging because of better survival and local control in diseases which are traditionally resistant to radiotherapy and chemotherapy such as melanoma and renal cell carcinoma. Key Message: We propose a new paradigm combining immunotherapy at a reduced dose and/or extended dosing intervals and hypofractionated radiotherapy for older patients with selected cancer which needs to be tested in future clinical trials.

Mutation HOXB13 c.853delT in Martinican prostate cancer patients.

BACKGROUND: In Martinique, prostate cancer (Pca) incidence rates are nowadays among the highest worldwide with a high incidence of early-onset and familial forms. Despite the demonstration of a strong familial component, identification of the genetic basis for hereditary Pca is challenging. The HOXB13 germline variant G84E (rs138213197) was described in men of European descent with Pca risk. METHODS: To investigate the potential involvement of HOXB13 mutations in Martinique, we performed sequencing of the HOXB13 coding regions of 46 index cases with early-onset Pca (before the age of 51). Additional breast cancers and controls were performed. All cancer cases analyzed in this study have been observed in the context of genetic counseling. RESULTS: We identified a rare heterozygous germline variant c.853delT (p.Ter285Lysfs) rs77179853, reported only among patients of African ancestry with a minor allele frequency of 3.2%. This variant is a stop loss reported only among patients of African ancestry with a frequency of 0.2%. CONCLUSION: In conclusion, we think that this study provides supplementary arguments that HOXB13 variants are involved in Pca.

International cooperation in public health in Martinique: geostrategic utility for cancer surveillance in the Caribbean.

BACKGROUND: Cooperation in public health and in oncology in particular, is currently a major issue for the island of Martinique, given its geopolitical position in the Caribbean region. The region of Martinique shares certain public health problems with other countries of the Caribbean, notably in terms of diagnostic and therapeutic management of patients with cancer. We present here a roadmap of cooperation priorities and activities in cancer surveillance and oncology in Martinique. MAIN BODY: The fight against cancer is a key public health priority that features high on the regional health policy for Martinique. In the face of these specific epidemiological conditions, Martinique needs to engage in medical cooperation in the field of oncology within the Caribbean, to improve skills and knowledge in this field, and to promote the creation of bilateral relations that will help to improve cancer management in an international healthcare environment. CONCLUSIONS: These collaborative exchanges will continue throughout 2020 and will lead to the implementation of mutual research projects across a larger population basin, integrating e-health approaches and epidemiological e-cohorts.

Grade groups at diagnosis in African Caribbean men with prostate cancer: Results of a comparative study.

BACKGROUND: There are no comparative data on pathological predictors at diagnosis, between African Caribbean and Caucasian men with prostate cancer (PCa), in equal-access centers. The objective of this study was to evaluate the grade groups of an African Caribbean cohort, newly diagnosed with PCa on prostate biopsy, compared with a Caucasian French Metropolitan cohort. METHODS: A retrospective, a comparative study was conducted between 2008 and 2016 between the University Hospital of Martinique in the French Caribbean West Indies, and the Saint Joseph Hospital in Paris. Clinical, biological, and pathological data were collected at diagnosis. The primary outcome was the grade groups for Gleason score; the secondary outcome was the PCa detection rate. Multivariate analysis was performed using linear regression. RESULTS: Of the 1880 consecutive prostate biopsy performed in the African Caribbean cohort, 945 had a diagnosis of PCa (50.3%) and 500 of 945 in the French cohort (33.8%). African Caribbean patients were older (mean 68.5 vs 67.5 years; P = .028), had worse clinical stage (13.2% vs 5.2% cT3-4; P < .001) and higher median prostate-specific antigen (PSA) level (9.23 vs 8.32 ng/mL; P = .019). On univariate analysis, African Caribbean patients had worse pathological grade groups than French patients (P < .001). Nevertheless, after adjustment on age, stage, and PSA, there were no significant differences between the two cohorts (P = .903). CONCLUSION: African Caribbean patients presented higher PCa detection rate, and higher grade groups at diagnosis than French patients in equal-access centers on univariate analysis but not on multivariate analysis. African Caribbean patients with equivalent clinical and biological characteristics than Caucasian patients at diagnosis might expect the same prognosis for PCa.

Pattern of care of prostate cancer patients across the Martinique: results of a population-based study in the Caribbean.

BACKGROUND: The French West-Indies rank first for both prostate cancer incidence and mortality rates. Analyzing diagnostic and therapeutic procedures among patients with prostate cancer, using data from a population-based cancer registry, is essential for cancer surveillance and research strategies. METHODS: This retrospective observational cohort study was based on data from the Martinique Cancer Registry. Records of 452 patients diagnosed with prostate cancer in 2013 were retrieved from the registry. Data extracted were: socio-demographic and clinical characteristics, circumstances of diagnosis, PSA level at diagnosis, Gleason score and risk of disease progression. Stage at diagnosis and patterns of care among prostate cancer patients were analyzed. RESULTS: Mean age at diagnosis was 67 ± 8 years; 103 (28.5%) were symptomatic at diagnosis. Digital rectal exam was performed in 406 (93.8%). Clinical stage was available in 385 (85.2%); tumours were localized in 322/385 (83.6%). Overall, 17.9% were at low risk, 36.4% at intermediate and 31.9% at high risk; 13.8% were regional/metastatic cancers. Median PSA level at diagnosis was 8.16 ng/mL (range 1.4-5000 ng/mL). A total of 373 patients (82.5%) received at least one treatment, while 79 (17.5%) had active surveillance or watchful waiting. Among patients treated with more than one therapeutic strategy, the most frequent combination was external radiotherapy with androgen deprivation (n = 102, 22.6%). CONCLUSIONS: This study provides detailed data regarding the quality of diagnosis and management of patients with prostate cancer in Martinique. Providing data on prostate cancer is essential for the development of high-priority public health measures for the Caribbean.

Technical Note: A respiratory monitoring and processing system based on computer vision: prototype and proof of principle.

Monitoring and controlling respiratory motion is a challenge for the accuracy and safety of therapeutic irradiation of thoracic tumors. Various commercial systems based on the monitoring of internal or external surrogates have been developed but remain costly. In this article we describe and validate Madibreast, an in-house-made respiratory monitoring and processing device based on optical tracking of external markers. We designed an optical apparatus to ensure real-time submillimetric image resolution at 4 m. Using OpenCv libraries, we optically tracked high-contrast markers set on patients' breasts. Validation of spatial and time accuracy was performed on a mechanical phantom and on human breast. Madibreast was able to track motion of markers up to a 5 cm/s speed, at a frame rate of 30 fps, with submillimetric accuracy on mechanical phantom and human breasts. Latency was below 100 ms. Concomitant monitoring of three different locations on the breast showed discrepancies in axial motion up to 4 mm for deep-breathing patterns. This low-cost, computer-vision system for real-time motion monitoring of the irradiation of breast cancer patients showed submillimetric accuracy and acceptable latency. It allowed the authors to highlight differences in surface motion that may be correlated to tumor motion.v.

Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer.

BACKGROUND: In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed. METHODS: A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70 Gy (62.4-75 Gy). RESULTS: At a median follow-up of 14 months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications. CONCLUSIONS: IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications.

Twenty-five Years Overall Survival Prognostic Value of the Lymph Node Ratio in De Novo Metastatic Breast Cancer.

BACKGROUND/AIM: The lymph node ratio (LNR) indicates the number of involved lymph nodes divided by the number of lymph nodes found during axillary exploration. This study investigated the prognostic value of the LNR in de novo metastatic breast cancer (dnMBC). We hypothesized that LNR might predict long-term survival even in cases where the disease has already disseminated beyond the regional stage. PATIENTS AND METHODS: Patients with dnMBC were selected from the Surveillance, Epidemiology, and End Results (SEER) 9-registries database 1988-2012. Positive lymph nodes (npos) were categorized as pN0 (npos=0), pN1 (npos=1 to 3), pN2 (npos=4 to 9), and pN3 (npos≥10). The LNR was categorized as Lnr0 (LNR=0), Lnr1 (LNR=0.01 to 0.20), Lnr2 (LNR=0.21 to 0.65), and Lnr3 (LNR≥0.65). The prognostic values were compared using Gini's mean difference Δ of the restricted mean overall survival time (RMST) according to npos versus LNR groups. RESULTS: A total of 12,085 patients with dnMBC had LNR data. At 25 years follow-up, the npos RMSTs were 10.4, 5.1, 5.8, and 5.0 years, for pN0 to pN3, respectively. The npos Gini's Δ was 2.8 years (standard error ±0.2). The LNR RMSTs were 10.4, 9.9, 7.6, and 4.0 years for Lnr0 to Lnr3, respectively. Δ for LNR was 3.6 (±0.2) years. Among node positive cases, the LNR low-risk group had an RMST of 9.9 years, approaching node-negative cases, while the high-risk group had an RMST of 4.0 years. CONCLUSION: LNR identified different prognostic groups, suggesting a possible role of lymph node involvement as a marker of lymphangiogenesis or lymphatic changes in the immune microenvironment, which warrants further investigation in dnMBC.

Low-Dose Apalutamide in Nonmetastatic Castration-Resistant Prostate Cancer: A Case Report.

The effect of low-dose apalutamide in nonmetastatic castration-resistant prostate cancer is unknown. We report the observation of therapy being administered at 25% of the recommended dose in an 80-year-old patient. Despite treatment discontinuation during COVID lockdowns, he survived three years without evidence of metastasis. This case gently invites us to reflect on the possibility of low-dose apalutamide in the elderly.

Organ at risk dose-volume metrics in a series of hypofractionated breast radiotherapy with integrated boost.

Dose and volume metrics to organs at risk are used for evaluation and optimization in radiotherapy planning. However, the numerous choices of metrics can be confusing. In a series of patients treated with hypofractionation and an integrated boost for breast cancer, we aim to determine if a parsimonious selection of representative metrics can be identified. The dosimetries of 42 patients receiving 42 Gy to the breast, with or without nodal irradiation, and 51 Gy integrated boost to tumor bed in 15 fractions were reviewed. For each organ-heart, lungs, and contralateral breast-cumulative dose-volume histograms were used to extract values for 3 basic metric classes: Two additional classes were considered: Pearson correlation coefficient R was calculated between pairs of values within each basic class and with the 2 additional classes for each organ. The interquartile ranges of correlations for D.yy, Vrel.xx, and Vabs.xx were as follows: The mean dose correlated with all basic classes for the heart and lungs, and with dose D.yy and volumes at Vrel.10-Vabs.10 for the contralateral breast. The standard deviation correlated with Vrel.xx and Vabs.xx for the heart and lungs (R ≥ 0.70). Among the D.yy, D.50 (median dose) correlated with the mean and standard deviation for all organs (R = 0.65-0.96). The mean, standard deviation, and median doses were the preeminent correlators. These statistics appear to be parsimonious representatives of doses to organs. Further studies with other radiotherapy series will be necessary to validate these observations.

Immunotherapy and radiotherapy for older patients with locally advanced rectal cancer unfit for surgery or decline surgery: a practical proposal by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced rectal cancer is total neoadjuvant therapy followed by surgical resection. Current evidence suggests that selected patients may be able to delay or avoid surgery without affecting survival rates if they achieve a complete clinical response (CCR). However, for older cancer patients who are too frail for surgery or decline the surgical procedure, local recurrence may lead to a deterioration of patient quality of life. Thus, for clinicians, a treatment algorithm which is well tolerated and may improve CCR in older and frail patients with rectal cancer may improve the potential for prolonged remission and potential cure. Recently, immunotherapy with check point inhibitors (CPI) is a promising treatment in selected patients with high expression of program death ligands receptor 1 (PD- L1). Radiotherapy may enhance PD-L1 expression in rectal cancer and may improve response rate to immunotherapy. We propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced rectal cancer who are too frail for surgery or who decline surgery.

Immunotherapy and stereotactic body radiotherapy for older patients with non-metastatic renal cancer unfit for surgery or decline nephrectomy: practical proposal by the International Geriatric Radiotherapy Group.

The standard of care for non-metastatic renal cancer is surgical resection followed by adjuvant therapy for those at high risk for recurrences. However, for older patients, surgery may not be an option due to the high risk of complications which may result in death. In the past renal cancer was considered to be radio-resistant, and required a higher dose of radiation leading to excessive complications secondary to damage of the normal organs surrounding the cancer. Advances in radiotherapy technique such as stereotactic body radiotherapy (SBRT) has led to the delivery of a tumoricidal dose of radiation with minimal damage to the normal tissue. Excellent local control and survival have been reported for selective patients with small tumors following SBRT. However, for patients with poor prognostic factors such as large tumor size and aggressive histology, there was a higher rate of loco-regional recurrences and distant metastases. Those tumors frequently carry program death ligand 1 (PD-L1) which makes them an ideal target for immunotherapy with check point inhibitors (CPI). Given the synergy between radiotherapy and immunotherapy, we propose an algorithm combining CPI and SBRT for older patients with non-metastatic renal cancer who are not candidates for surgical resection or decline nephrectomy.

Immunotherapy and radiotherapy for older patients with invasive bladder cancer unfit for surgery or chemotherapy: practical proposal by the international geriatric radiotherapy group.

The standard of care for non-metastatic muscle invasive bladder cancer is either radical cystectomy or bladder preservation therapy, which consists of maximal transurethral bladder resection of the tumor followed by concurrent chemoradiation with a cisplatin-based regimen. However, for older cancer patients who are too frail for surgical resection or have decreased renal function, radiotherapy alone may offer palliation. Recently, immunotherapy with immune checkpoint inhibitors (ICI) has emerged as a promising treatment when combined with radiotherapy due to the synergy of those two modalities. Transitional carcinoma of the bladder is traditionally a model for immunotherapy with an excellent response to Bacille Calmette-Guerin (BCG) in early disease stages, and with avelumab and atezolizumab for metastatic disease. Thus, we propose an algorithm combining immunotherapy and radiotherapy for older patients with locally advanced muscle-invasive bladder cancer who are not candidates for cisplatin-based chemotherapy and surgery.

Brachytherapy Versus Stereotactic Body Radiotherapy for Cervical Cancer Boost: A Dosimetric Comparison.

BACKGROUND: The standard treatment for locally advanced cervical cancer involves chemo-radiation followed by brachytherapy. However, some patients are unable to undergo brachytherapy intensification. Recent advancements in radiation technology have provided several techniques, with stereotactic body radiation therapy (SBRT) theoretically able to mimic the dose distribution of brachytherapy with a high dose gradient. METHODS: We analyzed 20 high-dose-rate intra-cavity brachytherapy plans for women with cervical cancer and simulated an adjunctive stereotactic radiotherapy plan at the same doses used for brachytherapy (21 Gray [Gy] in three fractions). No planning tumoral volume (PTV) margin was added for SBRT dosimetry. We used the dose constraints for brachytherapy from the EMBRACE trial and the dose constraints for SBRT in three fractions. Dose distribution, maximum dose points on target volumes, bladder, rectum, and dose-volume histograms were compared between the two techniques. RESULTS: The mean volume of the high-risk clinical tumoral volume (CTV) was 64 cm3, and the mean volume of the intermediate-risk CTV was 93 cm3. The mean minimum dose received by 90% of the high-risk CTV (D90 CTV HR) was 17 Gy for brachytherapy versus 8.3 Gy for SBRT. The average minimum dose received by 90% of the intermediate-risk CTV (D90 CTV IR) was 7.5 Gy for brachytherapy versus 8.9 Gy for SBRT. The mean minimum dose delivered to 2cc of the bladder was 74.6 Gy for brachytherapy versus 84.7 Gy for SBRT. The mean minimum dose delivered to 2cc of the rectum was 71.8 Gy for brachytherapy versus 74.7 Gy for SBRT. CONCLUSION: We confirmed the dosimetric superiority of brachytherapy over SBRT in terms of target volume coverage and organ-at-risk sparing. Therefore, pending the results of further clinical studies, no current radiotherapy technique can replace brachytherapy for cervical cancer boost after external radiotherapy.

Lung-heart toxicity in a randomized clinical trial of hypofractionated image guided radiation therapy for breast cancer.

Background: TomoBreast hypothesized that hypofractionated 15 fractions/3 weeks image-guided radiation therapy (H-IGRT) can reduce lung-heart toxicity, as compared with normofractionated 25-33 fractions/5-7 weeks conventional radiation therapy (CRT). Methods: In a single center 123 women with stage I-II operated breast cancer were randomized to receive CRT (N=64) or H-IGRT (N=59). The primary endpoint used a composite four-items measure of the time to 10% alteration in any of patient-reported outcomes, physician clinical evaluation, echocardiography or lung function tests, analyzed by intention-to-treat. Results: At 12 years median follow-up, overall and disease-free survivals between randomized arms were comparable, while survival time free from alteration significantly improved with H-IGRT which showed a gain of restricted mean survival time of 1.46 years over CRT, P=0.041. Discussion: The finding establishes TomoBreast as a proof-of-concept that hypofractionated image-guided radiation-therapy can improve the sparing of lung-heart function in breast cancer adjuvant therapy without loss in disease-free survival. Hypofractionation is advantageous, conditional on using an advanced radiation technique. Multicenter validation may be warranted. Trial registration: https://clinicaltrials.gov/ct2/show/NCT00459628. Registered 12 April 2007.

Immunotherapy and Hypofractionated Radiotherapy in Older Patients with Locally Advanced Cutaneous Squamous-Cell Carcinoma of the Head and Neck: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

Cutaneous skin carcinoma is a disease of older patients. The prevalence of cutaneous squamous-cell carcinoma (cSCC) increases with age. The head and neck region is a frequent place of occurrence due to exposure to ultraviolet light. Surgical resection with adjuvant radiotherapy is frequently advocated for locally advanced disease to decrease the risk of loco-regional recurrence. However, older cancer patients may not be candidates for surgery due to frailty and/or increased risk of complications. Radiotherapy is usually advocated for unresectable patients. Compared to basal-cell carcinoma, locally advanced cSCC tends to recur locally and/or can metastasize, especially in patients with high-risk features such as poorly differentiated histology and perineural invasion. Thus, a new algorithm needs to be developed for older patients with locally advanced head and neck cutaneous squamous-cell carcinoma to improve their survival and conserve their quality of life. Recently, immunotherapy with checkpoint inhibitors (CPIs) has attracted much attention due to the high prevalence of program death ligand 1 (PD-L1) in cSCC. A high response rate was observed following CPI administration with acceptable toxicity. Those with residual disease may be treated with hypofractionated radiotherapy to minimize the risk of recurrence, as radiotherapy may enhance the effect of immunotherapy. We propose a protocol combining CPIs and hypofractionated radiotherapy for older patients with locally advanced cutaneous head and neck cancer who are not candidates for surgery. Prospective studies should be performed to verify this hypothesis.