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.

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.

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.

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.

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.

Impact of COVID-19 pandemic on older cancer patients: Proposed solution by the International Geriatric Radiotherapy Group.

Older cancer patients are disproportionally affected by the Coronavirus 19 (COVID-19) pandemic. A higher rate of death among the elderly and the potential for long-term disability have led to fear of contracting the virus in these patients. This fear can, paradoxically, cause delay in diagnosis and treatment that may lead to a poor outcome that could have been prevented. Thus, physicians should devise a policy that both supports the needs of older patients during cancer treatment, and serves to help them overcome their fear so they seek out to cancer diagnosis and treatment early. A combination of telemedicine and a holistic approach, involving prayers for older cancer patients with a high level of spirituality, may improve vaccination rates as well as quality of life during treatment. Collaboration between health care workers, social workers, faith-based leaders, and cancer survivors may be crucial to achieve this goal. Social media may be an important component, providing a means of sending the positive message to older cancer patients that chronological age is not an impediment to treatment.

Lung-Heart Outcomes and Mortality through the 2020 COVID-19 Pandemic in a Prospective Cohort of Breast Cancer Radiotherapy Patients.

We investigated lung-heart toxicity and mortality in 123 women with stage I-II breast cancer enrolled in 2007-2011 in a prospective trial of adjuvant radiotherapy (TomoBreast). We were concerned whether the COVID-19 pandemic affected the outcomes. All patients were analyzed as a single cohort. Lung-heart status was reverse-scored as freedom from adverse-events (fAE) on a 1-5 scale. Left ventricular ejection fraction (LVEF) and pulmonary function tests were untransformed. Statistical analyses applied least-square regression to calendar-year aggregated data. The significance of outliers was determined using the Dixon and the Grubbs corrected tests. At 12.0 years median follow-up, 103 patients remained alive; 10-years overall survival was 87.8%. In 2007-2019, 15 patients died, of whom 11 were cancer-related deaths. In 2020, five patients died, none of whom from cancer. fAE and lung-heart function declined gradually over a decade through 2019, but deteriorated markedly in 2020: fAE dipped significantly from 4.6-4.6 to 4.3-4.2; LVEF dipped to 58.4% versus the expected 60.3% (PDixon = 0.021, PGrubbs = 0.054); forced vital capacity dipped to 2.4 L vs. 2.6 L (PDixon = 0.043, PGrubbs = 0.181); carbon-monoxide diffusing capacity dipped to 12.6 mL/min/mmHg vs. 15.2 (PDixon = 0.008, PGrubbs = 0.006). In conclusion, excess non-cancer mortality was observed in 2020. Deaths in that year totaled one-third of the deaths in the previous decade, and revealed observable lung-heart deterioration.

Immunotherapy and Modern Radiotherapy Technique for Older Patients with Locally Advanced Head and Neck Cancer: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for locally advanced head and neck cancer is concurrent chemoradiation or postoperative irradiation with or without chemotherapy. Surgery may not be an option for older patients (70 years old or above) due to multiple co-morbidities and frailty. Additionally, the standard chemotherapy of cisplatin may not be ideal for those patients due to oto- and nephrotoxicity. Though carboplatin is a reasonable alternative for cisplatin in patients with a pre-existing hearing deficit or renal dysfunction, its efficacy may be inferior to cisplatin for head and neck cancer. In addition, concurrent chemoradiation is frequently associated with grade 3-4 mucositis and hematologic toxicity leading to poor tolerance among older cancer patients. Thus, a new algorithm needs to be developed to provide optimal local control while minimizing toxicity for this vulnerable group of patients. Recently, immunotherapy with check point inhibitors (CPI) has attracted much attention due to the high prevalence of program death-ligand 1 (PD-L1) in head and neck cancer. In patients with recurrent or metastatic head and neck cancer refractory to cisplatin-based chemotherapy, CPI has proven to be superior to conventional chemotherapy for salvage. Those with a high PD-L1 expression defined as 50% or above or a high tumor proportion score (TPS) may have an excellent response to CPI. This selected group of patients may be candidates for CPI combined with modern radiotherapy techniques, such as intensity-modulated image-guided radiotherapy (IM-IGRT), volumetric arc therapy (VMAT) or proton therapy if available, which allow for the sparing of critical structures, such as the salivary glands, oral cavity, cochlea, larynx and pharyngeal muscles, to improve the patients' quality of life. In addition, normal organs that are frequently sensitive to immunotherapy, such as the thyroid and lungs, are spared with modern radiotherapy techniques. In fit or carefully selected frail patients, a hypofractionated schedule may be considered to reduce the need for daily transportation. We propose a protocol combining CPI and modern radiotherapy techniques for older patients with locally advanced head and neck cancer who are not eligible for cisplatin-based chemotherapy and have a high TPS. Prospective studies should be performed to verify this hypothesis.

Is immunotherapy at reduced dose and radiotherapy for older patients with locally advanced non-small lung cancer feasible?-a narrative review by the international geriatric radiotherapy group.

Background and Objective: The standard of care for locally advanced non-small cell lung cancer (NSCLC) is either surgery followed by adjuvant chemotherapy with or without radiotherapy or concurrent chemotherapy and radiotherapy. However, older patients (70 years old or above) with multiple co-morbidities may not be able to tolerate the combined treatment due to its toxicity. Since lung cancer prevalence increases significantly with age, a new algorithm needs to be investigated to allow curative treatment for those with locally advanced disease. Methods: A literature search of the literature was conducted through PubMed and Google Scholar using search terms such as locally advanced NSCLC, older cancer patients, immunotherapy with check point inhibitors (CPI), and image-guided radiotherapy (IGRT). Abstracts were screened, full articles fitting the article topic were reviewed, and duplicated and non-English articles were excluded. Key Content and Findings: Recently, CPI has been introduced and proven effective for selected patients with increased program death ligand 1 (PD-L1) expression (50% or above). A reduced dose for CPI (RDCPI) may be as effective as a full dose and may decrease treatment cost. New radiation technique such as IGRT may also minimize radiotherapy complication through normal lung and cardiac sparing. Conclusions: IGRT and RDCPI may be an innovative option for older patients with locally advanced NSCLC and high PD-L1 expression and needs to be investigated in future prospective studies.

Overall survival of triple negative breast cancer in French Caribbean women.

To describe survival according to prognostic factors of women with breast cancer in French overseas territory (Martinique) during 2008-2017. We performed a Cox model for prognostic factors for OS in breast cancer patients. The cut-off date for the analysis was 13/10/2018. The main factors were demographic data, stage, hormone receptors (HR) status and HER2 status. Curves were compared with the log rank test to select candidate variables for the multivariate analysis. We included 1,708 patients; median age at diagnosis was 57 years. Triple negative breast cancer (TNBC) accounted for 20.9% (n = 332). Among the patients, 72.3% (n = 1015) had localised or local spread cancer. One-year OS was 95.2% and was 80.1% at 5 years. In TNBC, 1-year-survival was 90.4%, which fell to 70.1% at 5 years. Patients with metastatic disease at diagnosis had 1-year-survival of 74.5%, and 20.1% at 5 years. Multivariate analysis by Cox regression identified 4 factors significantly associated with an increased risk of death: metastatic disease at diagnosis (hazard ratio (HR) = 15, p<0.0001), TNBC (HR 2.84, p<0.0001), HR+/HER2- status (HR 2.05, p<0.0084) and age >75 years (HR 3.8, p<0.0001). This is the first study performed on breast cancer survival in Martinique. Our findings show that breast cancer has overall good prognosis in patients and also how prognosis factors are distributed in the population.

Low-Dose Enzalutamide in Metastatic Prostate Cancer-Longevity Over Conventional Survival Analysis.

BACKGROUND: Enzalutamide is an important drug in the treatment of prostate cancer. Standard dosing often requires dose reduction because of side effects. There is no information on survival outcomes with lower doses. We investigated the impact of starting enzalutamide at ≤ 50% dose on metastatic prostate cancer outcomes including patients' longevity. PATIENTS AND METHODS: Records of metastatic prostate cancer patients treated with enzalutamide at one center were retrospectively reviewed. Low-dose enzalutamide (≤80 mg/day) was compared with standard-dose (160 mg/day). The primary objective was to compute the restricted mean survival time (RMST - time scale) and restricted mean attained age (RMAA - age scale) using the Irwin method. Secondary objectives included overall survival (OS), progression-free survival (PFS), and PSA progression per PCWG3 criteria (PSA PFS). We used the logrank test and the ∆ difference between RMSTs for comparison. RESULTS: Of 111 patients treated, 32 received a low-dose and 79 the standard-dose. Low-dose patients had less prior abiraterone or chemotherapy (28.1% vs. 65.8%, P < .001); more testosterone assessment (65.6% vs. 40.5%, P = .016); poorer ECOG performance status (48.3% score ≥2 vs. 26.6%; P = .040), more comorbidities (75.9% vs. 46.3%; P = .010)) including increased cardiovascular disease (51.7% vs. 21.4%, P = .004). Baseline PSA value and doubling time at start of enzalutamide and distribution of metastases were similar between the groups. OS and PFS did not differ between low-dose and standard-dose. Patients on low-dose had a better longevity with significantly longer RMAA, 89.1 years, versus standard-dose RMAA of 83.8 years (∆ = 5.3 years, P = .003, logrank P = .025). In a subgroup analysis by age at start of enzalutamide, <75 versus ≥75 years old, longevity was also better with low-dose in younger patients (∆ = 2.9 years, P = .034, and older, ∆ = 3.3 years, P = .011). CONCLUSION: The longevity advantage and reduced adverse events seen in patients with prostate cancer treated with low-dose enzalutamide warrants further investigation.

Providing Patients with Locally Advanced Cervical Cancer Access to Brachytherapy: Experience from a Referral Network for Women Treated in Overseas France.

Image-guided adaptive brachytherapy (IGABT) is part of the standard of care for locally advanced cervical cancer (LACC). Access to IGABT is limited in many regions, thus leading to treatment care disparities. We report the experience of a referral network for women with LACC between radiotherapy facilities in Overseas France and Gustave Roussy. This is a retrospective review of patients with LACC referred to Gustave Roussy, for pulsed-dose-rate (PDR) image-guided adaptive BT after initial radiation therapy in the French overseas between 2014 and 2021. Sixty-four patients were eligible to receive IGABT. Overall treatment time (OTT) was 60.5 days (IQR: 51−68.5). The median follow-up time was 17 months. At two years, estimated probabilities of LC, progression-free survival, and overall survival (OS) were 94.6% (95% CI: 88.9−100.0%), 72.7% (95% CI: 61.1−86.5%), and 82.5% (95% CI: 72.0−94.5%). In multivariable analysis, a D90CTVHR < 85GyEQD2 and a CTVHR volume > 40 cm3 were significant for poorer PFS (p = 0.001 and p = 0.009, respectively) and poorer OS (p = 0.004 and p = 0.004). The centralization of this advanced technique to expert centers requires a well-defined workflow and appropriate dimensioning of resources to minimize OTT.

Is there utility for fluorine-18-fluorodeoxyglucose positron-emission tomography scan before surgery in breast cancer? A 15-year overall survival analysis.

BACKGROUND: The prognostic value of preoperative fluorine-18-fluorodeoxyglucose positron-emission tomography (18F-FDG PET) scan for determining overall survival (OS) in breast cancer (BC) patients is controversial. AIM: To evaluate the OS predictive value of preoperative PET positivity after 15 years. METHODS: We performed a retrospective search of the Universitair Ziekenhuis Brussel patient database for nonmetastatic patients who underwent preoperative PET between 2002-2008. PET positivity was determined by anatomical region of interest (AROI) findings for breast and axillary, sternal, and distant sites. The prognostic role of PET was examined as a qualitative binary factor (positive vs negative status) and as a continuous variable [maximum standard uptake value (SUVmax)] in multivariate survival analyses using Cox proportional hazards models. Among the 104 identified patients who received PET, 36 were further analyzed for the SUVmax in the AROI. RESULTS: Poor OS within the 15-year study period was predicted by PET-positive status for axillary (P = 0.033), sternal (P = 0.033), and combined PET-axillary/sternal (P = 0.008) nodes. Poor disease-free survival was associated with PET-positive axillary status (P = 0.040) and combined axillary/sternal status (P = 0.023). Cox models confirmed the long-term prognostic value of combined PET-axillary/sternal status [hazard ratio (HR): 3.08, 95% confidence interval: 1.42-6.69]. SUVmax of ipsilateral breast and axilla as continuous covariates were significant predictors of long-term OS with HRs of 1.25 (P = 0.048) and 1.54 (P = 0.029), corresponding to relative increase in the risk of death of 25% and 54% per SUVmax unit, respectively. In addition, the ratio of the ipsilateral axillary SUVmax over the contralateral axillary SUVmax was the most significant OS predictor (P = 0.027), with 1.94 HR, indicating a two-fold relative increase of mortality risk. CONCLUSION: Preoperative PET is valuable for prediction of long-term survival. Ipsilateral axillary SUVmax ratio over the uninvolved side represents a new prognostic finding that warrants further investigation.

Lung Restriction in Patients With Breast Cancer After Hypofractionated and Conventional Radiation Therapy: A 10-Year Follow-up.

PURPOSE: Previous studies in patients with breast cancer have shown acute radiation therapy-induced reductions of pulmonary diffusing capacity, essentially owing to lung volume restriction. We aimed to assess the long-term effect of 2 radiation therapy regimens, which differed in terms of radiation technique and dose fractionation, on lung function. METHODS AND MATERIALS: From a randomized controlled trial comparing conventional 3-dimensional conformal radiation therapy (CR) and hypofractionated tomotherapy (TT), 84 patients with breast cancer (age at inclusion 54 ± 10 [standard deviation] years) could be assessed at baseline, after 3 months, and after 1, 2, 3, and 10 years. Measurements included forced vital capacity, total lung capacity (TLC), and diffusing capacity (TLco). RESULTS: Radiation therapy-induced lung function changes over 10 years (Δ) were similar for both treatment arms, and in a patient subgroup with negligible history of respiratory disease or smoking (n = 57) these averaged: Δ forced vital capacity = -13 (± 9) percent predicted; ΔTLco = -14 (± 12) percent predicted; and ΔTLC = -11 (± 9) percent predicted. The only significant correlation was between V20 (lung volume exposed to dose exceeding 20 Gy) and ΔTLco (rho = -0.36; P = .007). In this subgroup, as well as in the entire patient cohort, the incurred pulmonary restriction in terms of TLC and TLco showed a greater decline at 3 months for CR versus TT. However, at 10 years, no significant difference could be detected between CR and TT (P = .9 for TLC and P = .2 for TLco in the entire patient cohort). Of the patients with normal TLC and TLco at baseline (ie, above lower limits of normal), respectively 94% and 96% were still normal 10 years later. CONCLUSIONS: In women with breast cancer, conventional 3-dimensional conformal radiation therapy and hypofractionated tomotherapy induce similar restrictive lung patterns during the course of a 10-year period, despite some treatment-dependent differences in the first 3 months. The large majority of women with normal lung function at baseline maintained a normal lung function status 10 years after radiation therapy, irrespective of treatment arm.

Gini's mean difference and the long-term prognostic value of nodal quanta classes after pre-operative chemotherapy in advanced breast cancer.

Gini's mean difference (GMD, mean absolute difference between any two distinct quantities) of the restricted mean survival times (RMSTs, expectation of life at a given time limit) has been proposed as a new metric where higher GMD indicates better prognostic value. GMD is applied to the RMSTs at 25 years time-horizon to evaluate the long-term overall survival of women with breast cancer who received neoadjuvant chemotherapy, comparing a classification based on the number (pN) versus a classification based on the ratio (LNRc) of positive nodes found at axillary surgery. A total of 233 patients treated in 1980-2009 with documented number of positive nodes (npos) and number of nodes examined (ntot) were identified. The numbers were categorized into pN0, npos = 0; pN1, npos = [1,3]; pN2, npos = [4,9]; pN3, npos ≥ 10. The ratios npnx = npos/ntot were categorized into Lnr0, npnx = 0; Lnr1, npnx = (0,0.20]; Lnr2, npnx = (0.20,0.65]; Lnr3, npnx > 0.65. The GMD for pN-classification was 5.5 (standard error: ± 0.9) years, not much improved over a simple node-negative vs. node-positive that showed a GMD of 5.0 (± 1.4) years. The GMD for LNRc-classification was larger, 6.7 (± 0.8) years. Among other conventional metrics, Cox-model LNRc's c-index was 0.668 vs. pN's c = 0.641, indicating commensurate superiority of LNRc-classification. The usability of GMD-RMSTs warrants further investigation.

Prone versus supine free-breathing for right-sided whole breast radiotherapy.

Prone setup has been advocated to improve organ sparing in whole breast radiotherapy without impairing breast coverage. We evaluate the dosimetric advantage of prone setup for the right breast and look for predictors of the gain. Right breast cancer patients treated in 2010-2013 who had a dual supine and prone planning were retrospectively identified. A penalty score was computed from the mean absolute dose deviation to heart, lungs, breasts, and tumor bed for each patient's supine and prone plan. Dosimetric advantage of prone was assessed by the reduction of penalty score from supine to prone. The effect of patients' characteristics on the reduction of penalty was analyzed using robust linear regression. A total of 146 patients with right breast dual plans were identified. Prone compared to supine reduced the penalty score in 119 patients (81.5%). Lung doses were reduced by 70.8%, from 4.8 Gy supine to 1.4 Gy prone. Among patient's characteristics, the only significant predictors were the breast volumes, but no cutoff could identify when prone would be less advantageous than supine. Prone was associated with a dosimetric advantage in most patients. It sets a benchmark of achievable lung dose reduction.Trial registration: ClinicalTrials.gov NCT02237469, HUGProne, September 11, 2014, retrospectively registered.

Stereotactic Body Radiotherapy and Immunotherapy for Older Patients with Oligometastases: A Proposed Paradigm by the International Geriatric Radiotherapy Group.

The standard of care for metastatic disease is systemic therapy. A unique subset of patients with limited metastatic disease defined as distant involvement of five anatomic sites or less (oligometastases) have a better chance of remission or improved survival and may benefit from local treatments such as surgery or stereotactic body radiotherapy (SBRT). However, to prevent further spread of disease, systemic treatment such as chemotherapy, targeted therapy, and hormonal therapy may be required. Older patients (70 years old or above) or physiologically frail younger patients with multiple co-morbidities may not be able to tolerate the conventional chemotherapy due to its toxicity. In addition, those with a good performance status may not receive optimal chemotherapy due to concern about toxicity. Recently, immunotherapy with checkpoint inhibitors (CPI) has become a promising approach only in the management of program death ligand 1 (PD-L1)-positive tumors. Thus, a treatment method that elicits induction of PD-L1 production by tumor cells may allow all patients with oligometastases to benefit from immunotherapy. In vitro studies have demonstrated that high dose of radiotherapy may induce formation of PD-L1 in various tumors as a defense mechanism against inflammatory T cells. Clinical studies also corroborated those observations. Thus, SBRT, with its high precision to minimize damage to normal organs, may be a potential treatment of choice for older patients with oligometastases due to its synergy with immunotherapy. We propose a protocol combining SBRT to achieve a minimum radiobiologic equivalent dose around 59.5 Gy to all tumor sites if feasible, followed four to six weeks later by CPI for those cancer patients with oligometastases. All patients will be screened with frailty screening questionnaires to identify individuals at high risk for toxicity. The patients will be managed with an interdisciplinary team which includes oncologists, geriatricians, nurses, nutritionists, patient navigators, and social workers to manage all aspects of geriatric patient care. The use of telemedicine by the team may facilitate patient monitoring during treatment and follow-up. Preliminary data on toxicity, local control, survival, and progression-free survival may be obtained and serve as a template for future prospective studies.

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.

Lymph Node Ratio after Neoadjuvant Chemotherapy for Stage II/III Breast Cancer: Prognostic Value Measured with Gini's Mean Difference of Restricted Mean Survival Times.

Restricted mean survival time (RMST), recommended for reporting survival, lacks a tool to evaluate multilevel factors. The potential of the Gini's mean difference of RMSTs (Δ) is explored in a comparison of a lymph node ratio-based classification (LNRc) versus a number-based classification (ypN) applied to stage II/III breast cancer patients who received neoadjuvant chemotherapy and underwent axillary dissection. Number of positive nodes (npos) classified patients into ypN0, npos = 0, ypN1, npos = [1,3], ypN2, npos = [4,9], and ypN3, npos ⩾ 10. Ratio npos/(number of nodes examined) of 0, (0,0.20], (0.20,0.65], and >0.65, classified patients into Lnr0 to Lnr3, respectively. Unadjusted and Cox-adjusted RMSTs were computed for the ypN and LNRc's. At a follow-up time horizon of 72 months for 114 node-negative and 254 node-positive patients, unadjusted ypN0-ypN3 RMSTs were 62.4-41.4 months, Δ = 11.9 months (95%CI: 7.4-16.9), and Lnr0-Lnr3 62.4 to 36.3 months, Δ = 14.0 months (95%CI: 10.1-18.1). Cox models' ypN1-ypN3 hazard ratios were 1.81-3.30, and Lnr1-Lnr3 1.52-4.39. Δ from Cox-fitted survival were ypN 8.1 months (95%CI: 5.9-10.5), LNRc 10.5 months (95%CI: 8.4-12.8). In conclusion, Gini's mean difference is applicable to well established data in keeping with the literature on LNRc. It provides an alternative view on the improvement gained with a lymph node ratio-classification over using a number-classification.