Clinical and pathological characterization of 158 consecutive and unselected oligometastatic breast cancers in a single institution.

PURPOSE: Data about incidence, biological, and clinical characteristics of oligometastatic breast cancer (OMBC) are scarce. However, these data are essential in determining optimal treatment strategy. Gaining knowledge of these elements means observing and describing large, recent, and consecutive series of OMBC in their natural history. METHODS: We collected data retrospectively at our institution from 998 consecutive patients diagnosed and treated with synchronous or metachronous metastatic breast cancer (MBC) between January 2014 and December 2018. The only criterion used to define OMBC was the presence of one to five metastases at diagnosis. RESULTS: Of 998 MBC, 15.8% were classified OMBC. Among these, 88% had one to three metastases, and 86.7% had only one organ involved. Bone metastases were present in 52.5% of cases, 20.9% had progression to lymph nodes, 14.6% to the liver, 13.3% to the brain, 8.2% to the lungs, and 3.8% had other metastases. 55.7% had HR+/HER2- OMBC, 25.3% had HER2+OMBC, and 19% had HR-/HER2- OMBC. The HR+/HER2- subtype statistically correlated with bone metastases (p = 0.001), the HER2+subtype with brain lesions (p = 0.001), and the HR-/HER2- subtype with lymph node metastases (p = 0.008). Visceral metastases were not statistically associated with any OMBC subtypes (p = 0.186). OMBC-SBR grade III was proportionally higher than in the ESME series of 22,109 MBC (49.4% vs. 35.1%, p < 0.001). CONCLUSION: OMBC is a heterogeneous entity whose incidence is higher than has commonly been published. Not an indolent disease, each subgroup, with its biological and anatomical characteristics, merits specific management.

Nomograms to predict late urinary toxicity after prostate cancer radiotherapy.

OBJECTIVE: To analyze late urinary toxicity after prostate cancer radiotherapy (RT): symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms. METHODS: Nine hundred and sixty-five patients underwent RT in seventeen French centers for localized prostate cancer. Median total dose was 70 Gy (range, 65-80 Gy), using different fractionations (2 or 2.5 Gy/day) and techniques. Late urinary toxicity and the corresponding symptoms (urinary frequency, incontinence, dysuria/decreased stream, and hematuria) were prospectively assessed in half of the patients using the LENT-SOMA classification. Univariate and multivariate Cox regression models addressed patient or treatment-related predictors of late urinary toxicity (≥grade 2). Nomograms were built up, and their performance was assessed. RESULTS: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, dysuria, and urinary incontinence rates were 15, 10, 5, 3 and 1 %, respectively. The 5-year (≥grade 3) urinary toxicity rate was 3 %. The following parameters significantly increased the 5-year risk of global urinary toxicity (≥grade 2): anticoagulant treatment (RR = 2.35), total dose (RR = 1.09), and age (RR = 1.06). Urinary frequency was increased by the total dose (RR = 1.07) and diabetes (RR = 4). Hematuria was increased by anticoagulant treatment (RR = 2.9). Dysuria was increased by the total dose (RR = 1.1). Corresponding nomograms and their calibration plots were generated. Nomogram performance should be validated with external data. CONCLUSIONS: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.

High-Dose-Rate Brachytherapy for Treatment of Facial Skin Cancers: Local Control, Toxicity, and Quality of Life in 67 Patients.

While treatment of localized cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) is based on surgery, brachytherapy, which delivers a high dose of radiation to tumor tissue while sparing healthy tissue, is an alternative. Since the withdrawal of iridium wires from the market, brachytherapy has mainly been performed with high-dose-rate iridium-192 (HDR). This study evaluated the efficacy of HDR brachytherapy in terms of local control, survival, toxicity, and quality of life in patients with facial periorificial cutaneous SCC or BCC treated in our center between 2015 and 2021. Sixty-seven patients were treated for SCC (n = 49) or BCC (n = 18), on the nose (n = 29), lip (n = 28), eyelid (n = 7), or ear (n = 3). The majority had Tis or T1 tumors (73.1%). After a median follow-up of 28 months, 8 patients had a local recurrence. The local control rate at 3 years was 87.05% (95% CI 74.6-93.7). All patients developed grade 1-2 acute radio-mucositis or radiodermatitis and one experienced reversible grade 3 acute radio-mucositis. Of the 27 patients who completed the quality-of-life questionnaire, 77.8% recommended the treatment. This study confirms that HDR brachytherapy for facial cutaneous carcinomas provides good local control, good tolerance, and satisfactory functional outcome.

Deferred permanent prostate seed brachytherapy does not affect PSA outcome: results from a large retrospective cohort.

INTRODUCTION: To examine the outcome of deferred permanent seed brachytherapy (BT) for localized low or intermediate risk prostate cancer in order to identify predictors of delayed therapy (DT). MATERIALS AND METHODS: We studied 714 patients treated with BT with or without external radiotherapy. DT was defined as no treatment for > 350 days after the first biopsy with cancer. Factors influencing DT were analyzed. PSA outcome was assessed only in patients with a follow up ≥ 24 months. Patients with DT were compared to patients treated < 350 days using non-parametric tests. Multivariate analysis was performed using linear-regression analysis. RESULTS: BT was deferred in 125 patients (17.5%) for a median of 607 days (IQR 445-926). Patients with DT were older (71 years versus 69 years, p = 0.04) and had significantly less aggressive disease (percentage of positive biopsies, T1 disease, Gleason 6) on univariate analysis. On multivariate analysis, age (p = 0.01) and Gleason score (p = 0.05) were predictive for DT. Median (range) PSA follow up for DT patients was 36 months (24-78). The rate of patients with DT attaining a PSA at last follow up of < 0.2 ng/mL, < 0.5 ng/mL and ≤ 1 ng/mL was 53%, 73 % and 95%, respectively; only one patient (1.6 %) had biochemical failure (p = 0.61 compared to immediate BT). Multivariate analysis showed that age was predictive (p = 0.02) for a nadir of < 0.5 ng/mL and < 0.2 ng/mL (p = 0.017) and T-stage for a PSA < 0.2 ng/mL (p = 0.04). CONCLUSIONS: This is the largest analysis of the effects of deferred BT showing a promising rate of early PSA response.

Systemic treatment with or without ablative therapies in oligometastatic breast cancer: A single institution analysis of patient outcomes.

PURPOSE: Local ablative treatment (LAT) is increasingly combined with systemic therapy in oligometastatic breast cancer (OMBC), without a high-level evidence to support this strategy. We evaluated the addition of LAT to systemic treatment in terms of progression-free survival (PFS) and overall survival (OS). Secondary endpoints were local control (LC) and toxicity. We sought to identify prognostic factors associated with longer OS and PFS. METHODS AND MATERIALS: We identified consecutive patients treated between 2014 and 2018 for synchronous or metachronous OMBC (defined as ≤ 5 metastases). LAT included stereotactic body radiation therapy (SBRT) and volumetric modulated arc therapy (VMAT), surgery, cryotherapy and percutaneous radiofrequency ablation (PRA). PFS and OS were calculated, and Cox regression models analyzed for potential predictors of survival. RESULTS: One hundred two patients were included (no-LAT, n = 62; LAT, n = 40). Sixty-four metastases received LAT. Median follow-up was 50.4 months (95% CI [44.4; 53.4]). One patient experienced grade 3 toxicity in the LAT group. Five-year PFS and OS were 34.75% (95% CI [24.42-45.26]) and 63.21% (95% CI [50.69-73.37]) respectively. Patients receiving both LAT and systemic therapy had longer PFS and OS than those with no-LAT ([HR 0.39, p = 0.002]) and ([HR 0.31, p = 0.01]). The use of LAT, HER2-positive status and hormone-receptor positivity were associated with longer PFS and OS whereas liver metastases led to worse PFS. CONCLUSIONS: LAT was associated with improved outcomes in OMBC when added to systemic treatment, without significantly increasing toxicity. The prognostic factors identified to extend PFS and OS may help guide clinicians in selecting patients for LAT.

Helical tomotherapy for post-mastectomy radiation therapy with or without breast implant: a single institution experience.

Introduction: We report on our experience of using Helical Tomotherapy (HT) in the context of post-mastectomy radiation therapy (PMRT) with or without immediate implant-based breast Reconstruction (IBR). Material and methods: The study included a total of 173 patients who underwent PMRT with HT between 2013 and 2015 in our institution (87 immediate breast reconstructions with retropectoral implants (IBR + ), 86 without reconstructions (IBR-)). The chest wall target volume included subcutaneous tissue and pectoralis muscle and excluded the posterior region of the implant as well as the ribs. Results: Median time to initiation of the first adjuvant treatment from mastectomy was similar between the two groups (p = 0.134). Dose coverage to the chest wall was significantly improved for the IBR + group (V95% = 95.1 % versus 92.0 %; p < 0.0001). The irradiated volume of the ipsilateral lung was significantly decreased in the IBR + group with a median V20Gy of 11.6 %, compared to 15.2 % for the control group (p < 0.0001). The median heart V15Gy was also significantly lower in the IBR + group than in the control group (1.7 vs 2.5 %; p = 0.0280). The reconstruction failure rate was 14.9% (n = 13). After a median follow-up of 65 months, loco regional recurrence rate was low in both groups: 3 patients (3.4%) in the IBR + group and 5 patients (5.8%) in the control group, without any local recurrence in the posterior part of the implant. Conclusions: The presence of a breast implant reduces cardiac and pulmonary doses during Tomotherapy irradiation, without compromising oncological outcomes.

Preliminary experience of whole-brain radiation therapy (WBRT) in breast cancer patients with brain metastases previously treated with bevacizumab-based chemotherapy.

We report our experience of bevacizumab-based chemotherapy (BBCT) followed by whole-brain radiation therapy (WBRT) for breast cancer (BC) patients (pts) with inoperable brain metastases (BM) or who refused surgery. This is a retrospective study of seven metastatic BC pts treated at the Institut Curie with at least one course of BBCT before WBRT, with a delay of ≤ 12 months between the two treatments. Toxicity was scored according to the common terminology criteria for adverse events (v4. 2010). Median age was 56 years (41-65). Median follow-up was 5.9 months (0.4-24.6). The median dose of bevacizumab was 10 mg/kg. Median number of cycles BBCT was six (5-17). Different chemotherapy regimens were used, the most common combination was paclitaxel-bevacizumab. WBRT was delivered in ten fractions, five fractions/week, for two weeks, to a total of 30 Gy. One pt underwent stereotactic radio surgery (SRS) after WBRT. No pt received BBCT during RT. Most common reported side-effects were nausea (n = 4), headache (n = 3), vomiting (n = 1), and vertigo (n = 3). All pts had mild or moderate grade ≤ 2 neurologic toxicity. There were no radiological signs of necrosis or cerebral ischemia. BBCT before WBRT was not associated with severe brain toxicity. Because of the limited number of pts, the different BBCT regimens, and important delays between treatments, these results must be confirmed prospectively.

Intracranial Treatment in Melanoma Patients with Brain Metastasis Is Associated with Improved Survival in the Era of Immunotherapy and Anti-BRAF Therapy.

Metastatic melanoma patients are at high risk of brain metastases (BM). Although intracranial control is a prognostic factor for survival, impact of local (intracranial) treatment (LT), surgery and/or radiotherapy (stereotactic or whole brain) in the era of novel therapies remains unknown. We evaluated BM incidence in melanoma patients receiving immune checkpoint inhibitors (ICI) or anti-BRAF therapy and identified prognostic factors for overall survival (OS). Clinical data and treatment patterns were retrospectively collected from all patients treated for newly diagnosed locally advanced or metastatic melanoma between May 2014 and December 2017 with available BRAF mutation status and receiving systemic therapy. Prognostic factors for OS were analyzed with univariable and multivariable survival analyses. BMs occurred in 106 of 250 eligible patients (42.4%), 64 of whom received LT. Median OS in patients with BM was 7.8 months (95% CI [5.4-10.4]). In multivariable analyses, LT was significantly correlated with improved OS (HR 0.21, p < 0.01). Median OS was 17.3 months (95% CI [8.3-22.3]) versus 3.6 months (95% CI [1.4-4.8]) in patients with or without LT. LT correlates with improved OS in melanoma patients with BM in the era of ICI and anti-BRAF therapy. The use of LT should be addressed at diagnosis of BM while introducing systemic treatment.

Diagnosis, biology and epidemiology of oligometastatic breast cancer.

Does oligometastatic breast cancer (OMBC) deserve a dedicated treatment? Although some authors recommend multidisciplinary management of OMBC with a curative intent, there is no evidence proving this strategy beneficial in the absence of a randomized trial. The existing literature sheds little light on OMBC. Incidence is unknown; data available are either obsolete or biased; there is no consensus on the definition of OMBC and metastatic sites, nor on necessary imaging techniques. However, certain proposals merit consideration. Knowledge of eventual specific OMBC biological characteristics is limited to circulating tumor cell (CTC) counts. Given the data available for other cancers, studies on microRNAs (miRNAs), circulating tumor DNA (ctDNA) and genomic alterations should be developed Finally, safe and effective therapies do exist, but results of randomized trials will not be available for many years. Prospective observational cohort studies need to be implemented.

Laparoscopic closure of the pouch of Douglas by a peritoneal running suture. A minimally invasive and prosthetic-free technique to prevent excessive dose delivery to the small bowel during pelvic irradiation for prostate cancer.

BACKGROUND AND PURPOSE: Prostate radiotherapy relies on the delivery of high doses that can be obstructed when a small bowel loop descends in the pelvis. We present a laparoscopic minimally invasive prosthetic-free technique closing the Douglas' pouch with a peritoneal running suture to cordon off the bowel from the pelvis and hence allow optimal irradiation. MATERIALS AND METHODS: Prostate cancer patients referred for radiotherapy and whose planning-CT revealed a bowel loop trapped in the pelvis were proposed the procedure, followed by a new planning-CT. This proof-of-concept study reports postoperative follow-up and dosimetric benefits. RESULTS: The procedure was performed in ten patients (2016-2020) as a same-day surgery for nine. Median operative time was 34 min (range 22-50) and no relevant intraoperative complication occurred. The third patient of the series presented a small bowel hernia through the peritoneal suture at the 15th postoperative day requiring a laparotomic desincarceration without major consequences. Regarding the small bowel, median D1cc (dose to 1 cc) was 65.5 Gy and 55.5 Gy (p = 0.005) before and after procedure. Median V60 (volume receiving ≥60 Gy) was 10.2 cc and 0.0 cc (p = 0.005). In the immediate vicinity of the small bowel (5 mm), median D1cc was 68.3 Gy and 57.7 Gy (p = 0.005). Radiotherapy was safely delivered to all patients. CONCLUSION: Laparoscopic closure of the Douglas' pouch by a peritoneal suture is an efficient technique to cordon off inconvenient ectopic small bowel loops. It prevents excessive bowel irradiation and hence facilitates curative prostate radiotherapy. The technique could be applied to other pelvic malignancies.

PD-1 inhibitors might limit the development of brain metastases in patients with advanced melanoma.

Brain metastases are a common and severe complication potentially leading to death in patients with metastatic melanoma. Immunotherapy and targeted therapy have significantly improved progression-free survival (PFS) and overall survival (OS) in patients with advanced melanoma. Few studies focus on patients with central nervous system (CNS) metastases, and these patients are often excluded and have a poor prognosis. It has been suggested that immunotherapy could reduce the incidence of brain metastases. We tested this hypothesis in a retrospective bicentric study. We performed a retrospective, bicentric descriptive analysis on a cohort of 293 patients treated for metastatic melanoma between May 2014 and October 2017 (Toulouse, N = 202; Limoges, N = 91). Patients with brain metastasis at diagnosis were excluded from the analysis. Patients were separated into two groups according to the first line of treatment: immunotherapy [immune checkpoint inhibitor (ICI)] vs other and anti-PD-1 vs other. The primary endpoint was the cumulative incidence of brain metastases, and secondary endpoints were OS and PFS. At 12 months, the cumulative incidence of brain metastases was 13.78% in the ICI group [95% confidence interval (CI) 9.14-19.36] and 27.26% in the other group (95% CI 19.38-35.71), P = 0.004. The cumulative incidence was 9.49% in the anti-PD-1 group (95% CI 5.43-14.90) vs 30.11% in the other group (95% CI 22.59-37.97), P < 0.0001. In multivariable analysis (model with 277 patients), anti-PD-1 reduced the risk of brain metastases by almost 70% (hazard ratio = 0.29, 95% CI 0.15-0.56, P < 0.0001). The use of ICI (anti-PD-1/PD-L1) in advanced melanomas without initial brain metastasis shows a protective effect and prevents their occurrence.

Survival estimation of melanoma patients with brain metastasis using the Melanoma-molGPA score: external validation from a French cohort.

While immunotherapies and targeted therapies such as BRAF inhibitors have improved the prognosis, BM is still associated with poor outcome and a short survival. Metastatic melanoma patients are a heterogeneous subgroup with variable prognosis. As several prospective clinical trials have addressed the question of optimal therapy for these patients, an accurate validated selection tool is needed. Melanoma molecular graded prognostic assessment (Melanoma-molGPA) is a new prognostic score for BM melanoma patients. We decided to perform an external validation of this score. All consecutive patients treated between May 2014 and December 2017 for a newly diagnosed locally advanced or metastatic melanoma with available status for BRAF mutation were identified. Melanoma mol-GPA was applied in each patient with BM and correlated to overall survival. One hundred patients were included. Median follow-up was 27.8 months. Distribution for the Melanoma-molGPA groups GPA 0-1, GPA 1.5-2, GPA 2.5-3 and GPA 3.5-4 were as follows: 23, 51, 24 and 2.0%, respectively. Subgroups GPA 2.5-3 and 3.5-4 were combined. Median overall survival for groups GPA 0-1, 1.5-2 and 2.5-4.0 was 4.2, 6.9 and 18.4 months, respectively, P = 0.0032. Our study is the most recent, and with the largest cohort, to validate the Melanoma-molGPA score as an accurate and reproducible score for estimating overall survival. As several prospective clinical trials are addressing the issue of optimal therapy including the impact of local treatment for these patients, the Melanoma-molGPA is a useful tool in BM melanoma patients.

Concurrent radiotherapy for patients with metastatic melanoma and receiving anti-programmed-death 1 therapy: a safe and effective combination.

A combination of immune-checkpoint inhibitors and radiation therapy (RT) represents a promising therapeutic strategy in part mediated by the abscopal effect, but clinical experience related to this combination remains scarce. Clinical data and patterns of treatment were retrospectively collected from all consecutive patients with metastatic melanoma and receiving programmed-death 1 (PD-1) immune-checkpoint inhibitors. Survival data, best overall response, and acute and delayed toxicities (graded according to Common Terminology Criteria for Adverse Events, v 4.3) were compared between patients receiving concurrent RT (IR) or no irradiation (NIR). Fifty-nine patients received anti-PD-1 immunotherapy [pembrolizumab (n=28) or nivolumab (n=31)] between August 2014 and December 2015 at our institution. Among these, 29% (n=17) received palliative RT for a total of 21 sites, with a mean dose of 30 Gy delivered in 10 fractions. Acute and late toxicity profiles were similar in the two groups. After a 10-month median follow-up, the objective response rate (complete or partial response) was significantly higher in the IR group versus the NIR group (64.7 vs. 33.3%, P=0.02) and one complete responder after RT was compatible with an abscopal effect. The 6-month disease-free survival and overall survival rates for the NIR group versus the IR group were 49.7 versus 64.7% (P=0.32) and 58.8 versus 76.4% (P=0.42), respectively. We report here that the combination of RT and anti-PD-1 immunotherapy is well tolerated and leads to a significant higher tumor response rate within and outside the irradiated field, which is emphasized by the first reported case of an abscopal effect in solid tumors.

Nomogram to predict rectal toxicity following prostate cancer radiotherapy.

BACKGROUND: To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction. METHODS: In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups. RESULTS: Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3-0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0-1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1-10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3-0.8, p<0.01). Based on these three parameters, a nomogram was generated. CONCLUSIONS: Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique.

Intensity-modulated radiation therapy from 70Gy to 80Gy in prostate cancer: six- year outcomes and predictors of late toxicity.

OBJECTIVE: To report grade ≥2 overall late rectal and urinary toxicities in patients (pts) with prostate cancer treated by intensity-modulated radiotherapy (IMRT) at 3 dose-levels. Identify predictors of radiation toxicity and report biochemical progression free survival (bPFS). METHODS: A total of 277 pts were treated with 70Gy (10.8%), 74Gy (63.9%) and 80 Gy (25.3%) using IMRT without pelvic irradiation were analyzed. Short or long-course androgen deprivation therapy (ADT) was allowed in 46.1% of pts. The toxicity was described using the Common Terminology Criteria for Adverse Events (CTCAE) v4.0 scale. Cox regression models addressed demographics, disease and dosimetry characteristics as potential predictors of late grade ≥2 toxicity after adjusting for other modifying factors. RESULTS: The median follow-up was 77 months (range 15; 150). There was no grade ≥4 toxicity. The 5-year cumulative rate of grade ≥2 late rectal and urinary toxicities was 6.3% (95% CI = 3.8%; 10.3%) and 25.3% (95% CI = 19.8%; 31.8%) respectively. In multivariate analysis, only the dose (80Gy vs 74 and 70Gy) was found to increase the risk of rectal toxicity (HR = 2.96 [1.07; 8.20]). For pts receiving 74 Gy, International Prostate Symptom Score (IPSS) at baseline ≥8 (HR = 2.40 [1.08; 5.35]) and dose ≥73Gy delivered in more than 2% of bladder (D2%) were found to be predictors of bladder toxicity (HR = 3.29 [1.36; 7.98]). The 5-year biochemical relapse free survival was 81.0% [74.5%; 86.0%] in the entire population, 97.5% [83.5%; 99.6%] in the low risk group, 84.9% [76.7%; 90.3%] in the intermediate risk group and 66.4% [51.8%; 77.4%] in the high-risk group. D'Amico low (HR = 0.09 [0.01; 0.69]) and intermediate risk groups (HR = 0.50 [0.28; 0.88]) as well as PSA nadir ≥0.2 ng/ml (HR = 1.79 [1.01; 3.21]) were predictive of biochemical relapse. CONCLUSIONS: The rate of late rectal toxicity increased with higher doses, while Dmax ≥74Gy, D2% ≥ 73Gy for bladder wall and baseline IPSS ≥8 increased late urinary toxicity.

Random forests to predict rectal toxicity following prostate cancer radiation therapy.

PURPOSE: To propose a random forest normal tissue complication probability (RF-NTCP) model to predict late rectal toxicity following prostate cancer radiation therapy, and to compare its performance to that of classic NTCP models. METHODS AND MATERIALS: Clinical data and dose-volume histograms (DVH) were collected from 261 patients who received 3-dimensional conformal radiation therapy for prostate cancer with at least 5 years of follow-up. The series was split 1000 times into training and validation cohorts. A RF was trained to predict the risk of 5-year overall rectal toxicity and bleeding. Parameters of the Lyman-Kutcher-Burman (LKB) model were identified and a logistic regression model was fit. The performance of all the models was assessed by computing the area under the receiving operating characteristic curve (AUC). RESULTS: The 5-year grade ≥2 overall rectal toxicity and grade ≥1 and grade ≥2 rectal bleeding rates were 16%, 25%, and 10%, respectively. Predictive capabilities were obtained using the RF-NTCP model for all 3 toxicity endpoints, including both the training and validation cohorts. The age and use of anticoagulants were found to be predictors of rectal bleeding. The AUC for RF-NTCP ranged from 0.66 to 0.76, depending on the toxicity endpoint. The AUC values for the LKB-NTCP were statistically significantly inferior, ranging from 0.62 to 0.69. CONCLUSIONS: The RF-NTCP model may be a useful new tool in predicting late rectal toxicity, including variables other than DVH, and thus appears as a strong competitor to classic NTCP models.

Prostate volume changes during permanent seed brachytherapy: an analysis of intra-operative variations, predictive factors and clinical implication.

BACKGROUND: To determine prostate volume (Pvol) changes at 3 different time points during the course of I¹²5 permanent seed brachytherapy (PB). To assess the impact of these changes on acute urinary retention (AUR) and dosimetric outcome. METHODS: We analyzed 149 hormone-naïve patients. Measurements of the prostate volume were done using three-dimensional transrectal ultrasound (3D-TRUS) in the operating room before insertion of any needle (V1), after the insertion of 2 fixation needles with a harpoon (V2) and upon completion of the implant (V3). The quality of the implant was analyzed with the D90 (minimum dose in Grays received by 90% of the prostate volume) at day 30. RESULTS: Mean baseline prostate volume (V1) was 37.4 ± 9.6 cc. A volume increase of >5% was seen in 51% between V1-V2 (mean = 2.5 cc, p < 0.01), in 42% between V2-V3 (mean = 1.9 cc, p < 0.01) and in 71% between V1-V3 (mean = 4.5 cc, p < 0.01). Pvol changes caused by insertion of the fixation needles were not statistically different than those caused by the implant itself (p = 0.23).In multivariate linear regression analysis, baseline Pvol is predictive of Pvol changes between V2 and V1 and V3 and V1 but not between V3 and V2. The extent of prostate swelling had an influence on D90. An increase of 10% in prostate volume between V1 and V2 results in an increase of D90 at Day 30 by 11.7%. Baseline Pvol (V1) was the only predictor of the duration of urinary retention in both univariate and multivariate (p = 0.04) regression analysis. CONCLUSIONS: A large part of intraoperative swelling occurs already after the insertion of the fixation needles. This early prostate swelling predicts for D90 but not for AUR.

Unusually high prostate-specific antigen bounce after prostate brachytherapy: Searching for etiologic factors.

PURPOSE: Determine whether fat distribution, body mass index, or clinical and dosimetric factors are associated with prostate specific antigen (PSA) bounce (PSAb) of ≥1.6 ng/mL in patients treated with permanent seed (125)I prostate brachytherapy (PB). METHODS AND MATERIALS: We identified 23 patients with a PSAb of ≥1.6 ng/mL. For each patient with a bounce, at least one control with similar age (age ± 2 years, n=31) was identified. Control patients had to have no bounce (≤0.2 ng/mL) and a most recent PSA of <1 ng/mL. CT at Day 30 after PB was used to determine the volume of subcutaneous adipose tissue, visceral adipose tissue, and peri-prostatic fat. Univariate and multivariate logistic models were used to assess the association between PSAb and adipose tissue distribution and clinical and dosimetric factors. RESULTS: Mean patient age was 62.3 ± 5.3 years. Mean PSAb height was 2.7 ± 0.8 ng/mL, and mean time to bounce was 9.6 ± 4 months. More than 90% of the patients reached a PSA nadir before PSAb within 12 months post-PB. Patients showing PSAb were more likely to have a T1c disease vs. T2a (odds ratio = 18.87; 95% confidence interval: 2.32-454.55; p=0.019) and a lower seed activity per cc of prostate volume (odds ratio=0.02; 95% confidence interval=0.42-2.22; p=0.026). Neither fat distribution nor body mass index was associated with PSAb (p=0.11-0.597). CONCLUSIONS: Clinical and dosimetric factors play a role in PSAb of ≥1.6 ng/mL. Fat distribution is not associated with a PSAb. There is presently no satisfactory theory to explain the etiology of PSAb.

Helical tomotherapy for inoperable breast cancer: a new promising tool.

BACKGROUND: We investigated the feasibility of helical tomotherapy (HT) for inoperable large breast tumors, after failing to achieve adequate treatment planning with conformal radiation techniques. MATERIAL AND METHODS: Five consecutive patients with locally advanced breast cancer (LABC) were treated by preoperative HT. All patients received up-front chemotherapy before HT. Irradiated volumes included breast and nodal areas (45-50 Gy) in 4 patients. One patient received a simultaneous integrated boost (55 Gy) to gross tumor volume (GTV) without lymph node irradiation. Acute toxicity was assessed with Common Toxicity Criteria for Adverse Events v.4. Patients were evaluated for surgery at the end of treatment. RESULTS: Patients were staged IIB to IIIC (according to the AJCC staging system 2010). HT was associated in 4 patients with concomitant chemotherapy (5-fluorouracil and vinorelbine). Two patients were scored with grade 3 skin toxicity (had not completed HT) and one with grade 3 febrile neutropenia. One patient stopped HT with grade 2 skin toxicity. All patients were able to undergo mastectomy at a median interval of 43 days (31-52) from HT. Pathological partial response was seen in all patients. CONCLUSIONS: HT is feasible with acceptable toxicity profiles, potentially increased by chemotherapy. These preliminary results prompt us to consider a phase II study.