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.

Feasibility of image-guided radiotherapy and concurrent chemotherapy for locally advanced nonsmall cell lung cancer.

A retrospective review of 32 patients with stage III nonsmall cell lung cancer who underwent chemoradiation with image-guided radiotherapy (IGRT) was recorded. Acute grade 3-4 hematologic and esophageal toxicities developed in 6 and 13 patients respectively. At a median follow-up of 14.5 months, only one patient developed grade 3 pneumonitis. The median survival was estimated to be 17 months. Five patients (15%) developed loco-regional recurrences, and 17 patients (53%) distant metastases. Grade 3-4 toxicities remained significant during chemoradiation with IGRT. However, the reduced rate of severe pneumonitis despite a high tumor dose is encouraging and needs to be investigated in future prospective studies.

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.

Prioritizing environmental justice and equality: diesel emissions in southern California.

Existing environmental policies aim to reduce emissions but lack standards for addressing environmental justice. Environmental justice research documents disparities in exposure to air pollution; however, little guidance currently exists on how to make improvements or on how specific emission-reduction scenarios would improve or deteriorate environmental justice conditions. Here, we quantify how emission reductions from specific sources would change various measures of environmental equality and justice. We evaluate potential emission reductions for fine diesel particulate matter (DPM) in Southern California for five sources: on-road mobile, off-road mobile, ships, trains, and stationary. Our approach employs state-of-the-science dispersion and exposure models. We compare four environmental goals: impact, efficiency, equality, and justice. Results indicate potential trade-offs among those goals. For example, reductions in train emissions produce the greatest improvements in terms of efficiency, equality, and justice, whereas off-road mobile source reductions can have the greatest total impact. Reductions in on-road emissions produce improvements in impact, equality, and justice, whereas emission reductions from ships would widen existing population inequalities. Results are similar for complex versus simplified exposure analyses. The approach employed here could usefully be applied elsewhere to evaluate opportunities for improving environmental equality and justice in other locations.

Immunotherapeutic Strategies Targeting Breast Cancer Stem Cells.

Breast cancer is the most commonly diagnosed cancer in women and is a leading cause of cancer death in women worldwide. Despite the implementation of multiple treatment options, including immunotherapy, breast cancer treatment remains a challenge. In this review, we aim to summarize present challenges in breast cancer immunotherapy and recent advancements in overcoming treatment resistance. We elaborate on the inhibition of signaling cascades, such as the Notch, Hedgehog, Hippo, and WNT signaling pathways, which regulate the self-renewal and differentiation of breast cancer stem cells and, consequently, disease progression and survival. Cancer stem cells represent a rare population of cancer cells, likely originating from non-malignant stem or progenitor cells, with the ability to evade immune surveillance and develop resistance to immunotherapeutic treatments. We also discuss the interactions between breast cancer stem cells and the immune system, including potential agents targeting breast cancer stem cell-associated signaling pathways, and provide an overview of the emerging approaches to breast cancer stem cell-targeted immunotherapy. Finally, we consider the development of breast cancer vaccines and adoptive cellular therapies, which train the immune system to recognize tumor-associated antigens, for eliciting T cell-mediated responses to target breast cancer stem cells.

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.

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.

Retrospective study on the toxicity induced by stereotactic body radiotherapy: overview of the reunion experience on prostate cancer in elderly patients.

Introduction: Prostate cancer is the fourth most commonly diagnosed cancer among men worldwide. Various tools are used to manage disease such as conventional radiotherapy. However, it has been demonstrated that large prostate volumes were often associated with higher rates of genitourinary and gastrointestinal toxicities. Currently, the improvements in radiotherapy technology have led to the development of stereotactic body radiotherapy, which delivers higher and much more accurate radiation doses. In order to complete literature data about short-term outcome and short-term toxic effects of stereotactic body radiotherapy, we aimed to share our experience about gastrointestinal and genitourinary toxicities associated with stereotactic body radiotherapy in prostate cancer in patients over 70 years old. Methods: We retrospectively reviewed the medical records of elderly patients with prostate cancer treated between 2021 and 2022. The elderly patients were treated with a non-coplanar robotic stereotactic body radiotherapy platform using real-time tracking of implanted fiducials. The prostate, with or without part of the seminal vesicles, was treated with a total dose of 36.25 Gy delivered in five fractions, each fraction being administered every other day. Results: We analyzed a total of 80 elderly patients, comprising 38 low-, 37 intermediate- and 5 high-risk patients. The median follow-up duration was 12 months. We did not observe biochemical/clinical recurrence, distant metastasis, or death. Grade 2 acute genitourinary toxicity was observed in 9 patients (11.25%) and Grade 2 acute gastrointestinal toxicity in 4 patients (5.0%). We did not observe any grade 3 or more acute or late toxicities. Conclusion: Over the follow-up period, we noted a low frequency of gastrointestinal and genitourinary toxicities induced by stereotactic body radiotherapy in the context of prostate cancer in elderly patients. Therefore, stereotactic body radiotherapy seems to represent a promising treatment option for elderly patients, with acceptable acute toxicity.

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.

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.

Feasibility of image-guided radiotherapy based on helical tomotherapy to reduce contralateral parotid dose in head and neck cancer.

BACKGROUND: To evaluate the feasibility of image-guided radiotherapy based on helical Tomotherapy to spare the contralateral parotid gland in head and neck cancer patients with unilateral or no neck node metastases. METHODS: A retrospective review of 52 patients undergoing radiotherapy for head and neck cancers with image guidance based on daily megavoltage CT imaging with helical tomotherapy was performed. RESULTS: Mean contralateral parotid dose and the volume of the contralateral parotid receiving 40 Gy or more were compared between radiotherapy plans with significant constraint (SC) of less than 20 Gy on parotid dose (23 patients) and the conventional constraint (CC) of 26 Gy (29 patients). All patients had PTV coverage of at least 95% to the contralateral elective neck nodes. Mean contralateral parotid dose was, respectively, 14.1 Gy and 24.7 Gy for the SC and CC plans (p < 0.0001). The volume of contralateral parotid receiving 40 Gy or more was respectively 5.3% and 18.2% (p < 0.0001) CONCLUSION: Tomotherapy for head and neck cancer minimized radiotherapy dose to the contralateral parotid gland in patients undergoing elective node irradiation without sacrificing target coverage.

Effectiveness of prophylactic retropharyngeal lymph node irradiation in patients with locally advanced head and neck cancer.

BACKGROUND: The aim of the study is to assess the effectiveness of intensity-modulated radiotherapy (IMRT) or image-guided radiotherapy (IGRT) for the prevention of retropharyngeal nodal recurrences in locally advanced head and neck cancer. METHODS: A retrospective review of 76 patients with head and neck cancer undergoing concurrent chemoradiation or postoperative radiotherapy with IMRT or IGRT who were at risk for retropharyngeal nodal recurrences because of anatomic site (hypopharynx, nasopharynx, oropharynx) and/or the presence of nodal metastases was undertaken.The prevalence of retropharyngeal nodal recurrences was assessed on follow-up positron emission tomography (PET)-CT scans. RESULTS: At a median follow-up of 22 months (4-53 months), no patient developed retropharyngeal nodal recurrences. CONCLUSION: Prophylactic irradiation of retropharyngeal lymph nodes with IMRT or IGRT provides effective regional control for individuals at risk for recurrence in these nodes.

Rationale for Combing Stereotactic Body Radiation Therapy with Immune Checkpoint Inhibitors in Medically Inoperable Early-Stage Non-Small Cell Lung Cancer.

Stereotactic body radiation therapy (SBRT) has been widely adopted as an alternative to lobar resection in medically inoperable patients with lymph-node negative (N0) early-stage (ES) non-small cell lung cancer (NSCLC). Excellent in-field local control has been consistently achieved with SBRT in ES NSCLC ≤ 3 cm in size. However, the out-of-field control following SBRT remains suboptimal. The rate of recurrence, especially distant recurrence remains high for larger tumors. Additional systemic therapy is warranted in N0 ES NSCLC that is larger in size. Radiation has been shown to have immunomodulatory effects on cancer, which is most prominent with higher fractional doses. Strong synergistic effects are observed when immune checkpoint inhibitors (ICIs) are combined with radiation doses in SBRT's dose range. Unlike chemotherapy, ICIs can potentiate a strong systemic response outside of the irradiated field when combined with SBRT. Together with their less toxic nature, ICIs represent a very suitable class of systemic agents to be combined with SBRT when treating ES NSCLC with high-risk features, such as larger tumor size. In this review, we describe the rationale and emerging evidence, as well as ongoing investigations in this area.

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.

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.

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.

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.