Efficacy of stereotactic body radiotherapy and response prediction using artificial intelligence in oligometastatic gynaecologic cancer.

PURPOSE: We present a large real-world multicentric dataset of ovarian, uterine and cervical oligometastatic lesions treated with SBRT exploring efficacy and clinical outcomes. In addition, an exploratory machine learning analysis was performed. METHODS: A pooled analysis of gynecological oligometastases in terms of efficacy and clinical outcomes as well an exploratory machine learning model to predict the CR to SBRT were carried out. The CR rate following radiotherapy (RT) was the study main endpoint. The secondary endpoints included the 2-year actuarial LC, DMFS, PFS, and OS. RESULTS: 501 patients from 21 radiation oncology institutions with 846 gynecological metastases were analyzed, mainly ovarian (53.1%) and uterine metastases(32.1%).Multiple fraction radiotherapy was used in 762 metastases(90.1%).The most frequent schedule was 24 Gy in 3 fractions(13.4%). CR was observed in 538(63.7%) lesions. The Machine learning analysis showed a poor ability to find covariates strong enough to predict CR in the whole series. Analyzing them separately, in uterine cancer, if RT dose≥78.3Gy, the CR probability was 75.4%; if volume was <13.7 cc, the CR probability became 85.1%. In ovarian cancer, if the lesion was a lymph node, the CR probability was 71.4%; if volume was <17 cc, the CR probability rose to 78.4%. No covariate predicted the CR for cervical lesions. The overall 2-year actuarial LC was 79.2%, however it was 91.5% for CR and 52.5% for not CR lesions(p < 0.001). The overall 2-year DMFS, PFS and OS rate were 27.3%, 24.8% and 71.0%, with significant differences between CR and not CR. CONCLUSIONS: CR was substantially associated to patient outcomes in our series of gynecological cancer oligometastatic lesions. The ability to predict a CR through artificial intelligence could also drive treatment choices in the context of personalized oncology.

Adaptive Individualized high-dose preoperAtive (AIDA) chemoradiation in high-risk rectal cancer: a phase II trial.

PURPOSE: To evaluate the pathological complete response (pCR) rate of locally advanced rectal cancer (LARC) after adaptive high-dose neoadjuvant chemoradiation (CRT) based on 18 F-fluorodeoxyglucose positron emission tomography/computed tomography (18 F-FDG-PET/CT). METHODS: The primary endpoint was the pCR rate. Secondary endpoints were the predictive value of 18 F-FDG-PET/CT on pathological response and acute and late toxicity. All patients performed 18 F-FDG-PET/CT at baseline (PET0) and after 2 weeks during CRT (PET1). The metabolic PET parameters were calculated both at the PET0 and PET1. The total CRT dose was 45 Gy to the pelvic lymph nodes and 50 Gy to the primary tumor, corresponding mesorectum, and to metastatic lymph nodes. Furthermore, a sequential boost was delivered to a biological target volume defined by PET1 with an additional dose of 5 Gy in 2 fractions. Capecitabine (825 mg/m2 twice daily orally) was prescribed for the entire treatment duration. RESULTS: Eighteen patients (13 males, 5 females; median age 55 years [range, 41-77 years]) were enrolled in the trial. Patients underwent surgical resection at 8-9 weeks after the end of neoadjuvant CRT. No patient showed grade > 1 acute radiation-induced toxicity. Seven patients (38.8%) had TRG = 0 (complete regression), 5 (27.0%) showed TRG = 2, and 6 (33.0%) had TRG = 3. Based on the TRG results, patients were classified in two groups: TRG = 0 (pCR) and TRG = 1, 2, 3 (non pCR). Accepting p < 0.05 as the level of significance, at the Kruskal-Wallis test, the medians of baseline-MTV, interim-SUVmax, interim-SUVmean, interim-MTV, interim-TLG, and the MTV reduction were significantly different between the two groups. 18 F-FDG-PET/CT was able to predict the pCR in 77.8% of cases through compared evaluation of both baseline PET/CT and interim PET/CT. CONCLUSIONS: Our results showed that a dose escalation on a reduced target in the final phase of CRT is well tolerated and able to provide a high pCR rate.

Reproducibility and stability of spirometer-guided deep inspiration breath-hold in left-breast treatments using an optical surface monitoring system.

The aim of this study was to evaluate the reproducibility and stability of left breast positioning during spirometer-guided deep-inspiration breath-hold (DIBH) radiotherapy using an optical surface imaging system (AlignRT). The AlignRT optical tracking system was used to monitor five left-sided breast cancer patients treated using the Active Breathing Coordinator spirometer with DIBH technique. Treatment plans were created using an automated hybrid-VMAT technique on DIBH CTs. A prescribed dose of 60 Gy to the tumor bed and 50 Gy to the breast in 25 fractions was planned. During each treatment session, the antero-posterior (VRT), superior-inferior (LNG), and lateral (LAT) motion of patients was continuously recorded by AlignRT. The intra-breath-hold stability and the intra- and inter-fraction reproducibility were analyzed for all breath-holds and treatment fractions. The dosimetric impact of the residual motion during DIBH was evaluated from the isocenter shifts amplitudes obtained from the 50%, 90%, and 100% cumulative distribution functions of intra-fractional reproducibility. The positional variations of 590 breath-holds as measured by AlignRT were evaluated. The mean intra-breath-hold stability during DIBH was 1.0 ± 0.4 mm, 2.1 ± 1.9 mm, and 0.7 ± 0.5 mm in the VRT, LNG, and LAT directions, with a maximal value of 8.8 mm in LNG direction. Similarly, the mean intra-breath-hold reproducibility was 1.4 ± 0.8 mm, 1.7 ± 1.0 mm, and 0.8 ± 0.5 mm in the VRT, LNG, and LAT directions, with a maximal value of 4.1 mm in LNG direction. Inter-fractional reproducibility showed better reliability, with difference in breathing levels in all fractions of 0.3 mm on average. Based on tolerance limits corresponding to the 90% cumulative distribution level, gating window widths of 1 mm, 2 mm, and 5 mm in the LAT, VRT, and LNG directions were considered an appropriate choice. In conclusion, despite the use of a dedicated spirometer at constant tidal volume, a non-negligible variability of the breast surface position has been reported during breath-holds. The real-time monitoring of breast surface using surface-guided optical technology is strongly recommended.

Automated hybrid volumetric modulated arc therapy (HVMAT) for whole-breast irradiation with simultaneous integrated boost to lumpectomy area : A treatment planning study.

PURPOSE: To develop an automated treatment planning approach for whole breast irradiation with simultaneous integrated boost using an automated hybrid VMAT class solution (HVMAT). MATERIALS AND METHODS: Twenty-five consecutive patients with left breast cancer received 50 Gy (2 Gy/fraction) to the whole breast and an additional simultaneous 10 Gy (2.4 Gy/fraction) to the tumor cavity. Ipsilateral lung, heart, and contralateral breast were contoured as main organs-at-risk. HVMAT plans were inversely optimized by combining two open fields with a VMAT semi-arc beam. Open fields were setup to include the whole breast with a 2 cm flash region and to carry 80% of beams weight. HVMAT plans were compared with three tangential techniques: conventional wedged-field tangential plans (SWF), field-in-field forward planned tangential plans (FiF), and hybrid-IMRT plans (HMRT). Dosimetric differences among the plans were evaluated using Kruskal-Wallis one-way analysis of variance. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. RESULTS: No significant differences were found among the four techniques for both targets coverage. HVMAT plans showed consistently better PTVs dose contrast, conformity, and homogeneity (p < 0.001 for all metrics) and statistically significant reduction of high-dose breast irradiation. V55 and V60 decreased by 30.4, 26.1, and 20.8% (p < 0.05) and 12.3, 9.9, and 6.0% (p < 0.05) for SWF, FIF, and HMRT, respectively. Pretreatment dose verification reported a gamma pass-rate greater than the acceptance threshold of 95% for all HVMAT plans. In addition, HVMAT reduced the time for full planning optimization to about 20 min. CONCLUSIONS: HVMAT plans resulted in superior target dose conformity and homogeneity compared to other tangential techniques. Due to fast planning time HVMAT can be applied for all patients, minimizing the impact on human or departmental resources.

COVID-19 free oncologic surgical hub: The experience of reallocation of a gynecologic oncology unit during pandemic outbreak.

INTRODUCTION: During the SARS-CoV-2 pandemic, the majority of healthcare resources of the affected Italian regions were allocated to COVID-19 patients. Due to lack of resources and high risk of death, most cancer patients have been shifted to non-surgical treatments. The following reports our experience of a Gynaecologic Oncology Unit's reallocation of resources in a COVID-19 free surgical oncologic hub in order to guarantee standard quality of surgical activities. MATERIALS AND METHODS: This is a prospective observational study performed in the Gynaecologic Oncology Unit, on the outcomes of the reallocation of surgical activities outside the University Hospital of Bologna, Italy, during the Italian lockdown period. Here, we described our COVID-19 free surgical oncologic pathway, in terms of lifestyle restrictions, COVID-19 screening measures, and patient clinical, surgical and follow up outcomes. RESULTS: During the lockdown period (March 9th - May 4th, 2020), 83 patients were scheduled for oncological surgery, 51 patients underwent surgery. Compared to pre-COVID period, we performed the same activities: number of cases scheduled for surgery, type of surgery and surgical and oncological results. No cases of COVID-19 infection were recorded in operated patients and in medical staff. Patients were compliant and well accepted the lifestyle restrictions and reorganization of the care. CONCLUSIONSONCLUSIONS: Our experience showed that the prioritization of oncological surgical care and the allocation of resources during a pandemic in COVID-19 free surgical hubs is an appropriate choice to guarantee oncological protocols.

The role of radiotherapy in adult soft tissues sarcoma of the extremities.

Local management of adult soft tissue sarcoma of the extremities has evolved over the past decades. Until the 1970s, radical surgery (amputations) was the standard therapeutic procedure resulting in significant physical and psychological morbidity for the patients. In the present era, limb sparing surgery combined with radiotherapy represents the current standard of care for high grade and > 5 cm STSs. This approach guarantees high local control rate and function preservation. The aim of this paper is to summarize the current evidence for RT in STSs of the extremities. Outcomes, technical details (techniques, timing, dose, volumes of treatment) and the emerging role of RT in the management of oligometastatic disease will be analysed. Finally, results of the recent clinical trials testing new scenarios in RT of STSs will be described.

Radiotherapy of prostate cancer: impact of treatment characteristics on the incidence of second tumors.

BACKGROUND: It has been hypothesized that radiotherapy (RT) techniques delivering radiations to larger volumes (IMRT, VMAT) are potentially associated with a higher risk of second primary tumors. The aim of this study was to analyse the impact of RT technique (3D-CRT vs IMRT/VMAT) on the incidence of second tumors in prostate cancer (PCa) patients. METHODS: A retrospective study on 2526 previously irradiated PCa patients was performed. Patients were treated with 3D-CRT (21.3%), IMRT (68.1%), or VMAT (10.6%). Second tumors incidence was analysed in 3 categories: pelvic, pelvic and abdominal, and "any site". The correlation with RT technique was analysed using log-rank test and Cox's proportional hazard method. RESULTS: With a median follow-up of 72 months (range: 9-185), 92 (3.6%) cases of second tumors were recorded with 48 months (range: 9-152) median interval from RT. Actuarial 10-year second tumor free survival (STFS) was 87.3%. Ten-year STFS in patients treated with 3D-CRT and IMRT/VMAT was 85.8 and 84.5%, respectively (p: .627). A significantly higher 10-year cumulative incidence of second tumors in the pelvis was registered in patients treated with IMRT/VMAT compared to 3D-CRT (10.7% vs 6.0%; p: .033). The lower incidence of second pelvic cancers in patients treated with 3D-CRT was confirmed at multivariable analysis (HR: 2.42, 95%CI: 1.07-5.47, p: .034). CONCLUSIONS: The incidence of second pelvic tumors after RT of PCa showed a significant correlation with treatment technique. Further analyses in larger series with prolonged follow-up are needed to confirm these results.

Anorectal adenocarcinoma recurrence successfully treated with electrochemotherapy: a case report.

Anal canal adenocarcinoma is generally treated like rectal cancer. Surgery is the standard treatment in early stages and neoadjuvant chemoradiation in locally advanced tumors. Local recurrences treatment paradigm often depends on the previous therapies of either surgery or radiotherapy or systemic therapy. We present the case of a patient with tubulovillous adenocarcinoma of the anal canal which relapsed after chemoradiation. The patient refused salvage surgery and was treated with definitive electrochemotherapy under general anesthesia. Tumor electroporation performed with the insertion of three needles in the recurred site was preceded by an intravenous bolus of bleomycin. After the administered treatment, the patient showed a complete clinical response. A year after electrochemotherapy, the patient is free from local disease with excellent preservation of the sphincter function. Electrochemotherapy may be considered as an alternative to surgery in small lesion in the anorectal region when other approaches are excluded.

Randomized Pilot Trial of Percutaneous Posterior Tibial Nerve Stimulation Versus Medical Therapy for the Treatment of Low Anterior Resection Syndrome: One-Year Follow-up.

BACKGROUND: Low anterior resection syndrome is significantly associated with a deterioration in the quality of life, and its medical treatment is usually ineffective. OBJECTIVE: The aim of the present study was to establish the efficacy of percutaneous tibial nerve stimulation in treating this syndrome. DESIGN: This is a randomized pilot trial with 1-year follow-up. SETTINGS: The study was conducted in a specialized colorectal unit of a tertiary hospital. PATIENTS: Patients who underwent neoadjuvant chemoradiotherapy and low anterior rectal resection for cancer with low anterior resection syndrome score ≥21 and ileostomy closed at least 18 months earlier were included. INTERVENTIONS: Patients were randomly assigned to receive either percutaneous tibial nerve stimulation plus medical treatment (arm A, n = 6) or medical treatment (arm B, n = 6). Low anterior resection syndrome was assessed using symptom severity and disease-specific quality-of-life scores at baseline, at the end of treatment, and at 1-year follow-up. MAIN OUTCOME MEASURES: The primary outcome was a clinical response, defined as a reduction of the low anterior resection syndrome score. RESULTS: Only in group A low anterior resection syndrome score, fecal incontinence severity index, and obstructed defecation syndrome score improved significantly with treatment (35.8 ± 2.5 vs 29.0 ± 3.8 (p = 0.03); 36.8 ± 4.3 vs 18.5 ± 8.0 (p = 0.02); 10.3 ± 3.9 vs 8.0 ± 4.9 (p = 0.009)) and changes were observed in all domains of quality-of-life instruments. In both groups the symptom severity and quality-of-life scores at 1-year follow-up did not differ significantly from those recorded at the end of treatment. LIMITATIONS: The study had a small number of patients and it was underpowered to detect the within-group effect. CONCLUSIONS: Percutaneous tibial nerve stimulation could be an effective treatment for low anterior resection syndrome. Additional studies are warranted to investigate clinical effectiveness in low anterior resection syndrome. See Video Abstract at http://links.lww.com/DCR/B371. ESTUDIO PILOTO ALEATORIO DE ESTIMULACIÓN PERCUTÁNEA DEL NERVIO TIBIAL POSTERIOR VERSUS TERAPIA MÉDICA PARA EL TRATAMIENTO DEL SÍNDROME DE RESECCIÓN ANTERIOR BAJA: UN AÑO DE SEGUIMIENTO: El síndrome de resección anterior baja se asocia con un deterioro significativo en la calidad de vida y su tratamiento médico generalmente es ineficaz.El objetivo del presente estudio fue establecer la eficacia de la estimulación percutánea del nervio tibial en el tratamiento de este síndrome.Este es un estudio piloto aleatorio con 1 año de seguimiento.El estudio se realizó en una unidad colorrectal especializada de un hospital terciario.Se incluyeron pacientes que se sometieron a quimiorradioterapia neoadyuvante y resección rectal anterior baja por cáncer con puntaje de síndrome de resección anterior baja ≥ 21 e ileostomía cerrada al menos 18 meses antes.Los pacientes fueron asignados aleatoriamente para recibir estimulación percutánea del nervio tibial + tratamiento médico (brazo A, n = 6) o tratamiento médico (brazo B, n = 6). El síndrome de resección anterior baja se evaluó utilizando puntajes de la gravedad de los síntomas y de calidad de vida específicos de la enfermedad al inicio, al final del tratamiento y al año de seguimiento.El resultado primario fue una respuesta clínica, definida como una reducción de la puntuación del síndrome de resección anterior baja.Solo en el grupo A, el puntaje del síndrome de resección anterior baja, el índice de severidad de incontinencia fecal y el puntaje del síndrome de defecación obstruida mejoraron significativamente con el tratamiento (35.8 ± 2.5 vs 29 ± 3.8, p = 0.03; 36.8 ± 4.3 vs 18.5 ± 8.0, p = 0.02; 10.3 ± 3.9 vs 8.0 ± 4.9, p = 0.009, respectivamente) y se observaron cambios en todos los dominios de los instrumentos de calidad de vida. En ambos grupos, los puntajes de severidad de los síntomas y de calidad de vida al año de seguimiento no difirieron significativamente de los registrados al final del tratamiento.El estudio tuvo un pequeño número de pacientes y no logró suficiente poder para detectar el efecto dentro de grupo.La estimulación percutánea del nervio tibial podría ser un tratamiento efectivo para el síndrome de resección anterior baja. Se requieren estudios adicionales para investigar la efectividad clínica en el síndrome de resección anterior baja. Consulte Video Resumen http://links.lww.com/DCR/B371.

Palliative treatment with electrochemotherapy in recurrent or metastatic vaginal cancer.

OBJECTIVE: Vaginal metastases are very rare events with a poor prognosis. To improve the quality of life, local treatments should be considered. The aim of this study was to evaluate the role of electrochemotherapy as palliative treatment in vaginal cancer not amenable to standard treatments due to poor performance status, previous treatments, or advanced disease. METHODS: This is a prospective observational study on patients diagnosed with vaginal cancer and treated from January 2017 to December 2018 with palliative electrochemotherapy. We collected data on patients with vaginal cancer treated by electrochemotherapy with the aim of local control. Data regarding electrochemotherapy, hospital stay, adverse events, and patient outcomes were analyzed. Intravenous bleomycin was injected as a bolus in 2-3 min at a dose of 15 000 UI/m2 and electrical pulses started 8 min after chemotherapy. Electrochemotherapy response was defined according to the Response Evaluation Criteria in Solid Tumors. RESULTS: Five patients with vaginal recurrence (two squamous, two melanomas, and one leiomyosarcoma) and one with vaginal metastasis from intestinal adenocarcinoma received one treatment and two patients were re-treated. Imaging reported nodal metastasis (inguinal or pelvic) in two patients, distant metastases in two, and both node and distant metastasis in two patients, respectively. Response Evaluation Criteria in Solid Tumors showed a complete response in one patient, partial response in three patients, stable disease in one patient, and progressive disease in one patient, with an overall response rate of 67% and a clinical benefit rate (complete response, partial response, stable disease) of 83%. Two patients were re-treated and had a new response (partial response and stable disease, respectively). At last follow-up, two patients had died of the disease, two were alive with stable disease, one was alive with progressive disease, and one was alive without disease. Median post-electrochemotherapy overall survival was 12.9 months (range 1.6-26.9) and 1-year overall survival was 66.7%. CONCLUSIONS: This preliminary experience showed a tumor response or stabilization in 83% of patients requiring palliative management for vaginal cancer. Further studies are needed to evaluate treatment outcome in larger and prospective series.

Automated treatment planning as a dose escalation strategy for stereotactic radiation therapy in pancreatic cancer.

PURPOSE: To assess the feasibility of automated stereotactic volumetric modulated arc therapy (SBRT-VMAT) planning using a simultaneous integrated boost (SIB) approach as a dose escalation strategy for SBRT in pancreatic cancer. METHODS: Twelve patients with pancreatic cancer were retrospectively replanned. Dose prescription was 30 Gy to the planning target volume (PTV) and was escalated up to 50 Gy to the boost target volume (BTV) using a SIB technique in 5 fractions. All plans were generated by Pinnacle3 Autoplanning using 6MV dual-arc VMAT technique for flattened (FF) and flattening filter-free beams (FFF). An overlap volume (OLV) between the PRV duodenum and the PTV was defined to correlate with the ability to boost the BTV. Dosimetric metrics for BTV and PTV coverage, maximal doses for serial OARs, integral dose, conformation numbers, and dose contrast indexes were used to analyze the dosimetric results. Dose accuracy was validated using the PTW Octavius-4D phantom together with the 1500 2D-array. Differences between FF and FFF plans were quantified using the Wilcoxon matched-pair signed rank. RESULTS: Full prescription doses to the 95% of PTV and BTV can be delivered to patients with no OLV. BTV mean dose was >90% of the prescribed doses for all patients at all dose levels. Compared to FF plans, FFF plans showed significant reduced integral doses, larger number of MUs, and reduced beam-on-times up to 51% for the highest dose level. Despite plan complexity, pre-treatment verification reported a gamma pass-rate greater than the acceptance threshold of 95% for all FF and FFF plans for 3%-2 mm criteria. CONCLUSIONS: The SIB-SBRT strategy with Autoplanning was dosimetrically feasible. Ablative doses up to 50 Gy in 5 fractions can be delivered to the BTV for almost all patients respecting all the normal tissue constraints. A prospective clinical trial based on SBRT strategy using SIB-VMAT technique with FFF beams seems to be justified.

Definitive Radiotherapy in Invasive Vaginal Carcinoma: A Systematic Review.

AIM: This study systematically reviews the recent literature on the role of definitive radiotherapy (RT) in the management of vaginal cancer (VC) and presents comprehensive data on clinical outcomes and toxicity. METHODS: The authors performed a literature search using PubMed (2007-2016) to identify all prospective and retrospective studies that have been published on RT in invasive VC. RESULTS: Of the 199 identified studies, 13 met the inclusion criteria. All studies had a retrospective design. Overall, 793 patients (median, 45; range, 26-138) were included. A high heterogeneity was found across studies in terms of RT techniques, assessment criteria, and reported outcomes. The majority of the patients were treated with a combination of external beam RT and brachytherapy (74.2%). Acute and late grade ≥3 toxicity rates ranged from 0.0% to 24.4% (median, 8.7%) and from 0.0% to 22.5% (median, 12.8%), respectively. The 5-year local control rates ranged between 39% and 79%. The 5-year overall survival ranged between 34% and 71.0% (median, 63.5%). Early stage of the disease (International Federation of Gynecology and Obstetrics stages I-II vs. III-IV), small tumor size (<4 cm), previous hysterectomy, high pretreatment/treatment hemoglobin levels (≥12/12.5 mg/dL), and patients' age <70 or <64 years were correlated with better clinical outcomes. CONCLUSION: Only retrospective studies, in a limited number, have been published on RT in VC in the past decade, with significant heterogeneity in terms of treatment characteristic and evaluation criteria. Clinical results were strongly influenced by tumor stage. Prospective randomized studies are needed to improve patients' outcomes, especially in advanced-stage disease. IMPLICATIONS FOR PRACTICE: This study systematically reviews the recent literature on the role of definitive radiotherapy in the management of vaginal cancer and presents comprehensive data on clinical outcome and toxicity. The prognosis of patients is dismal, with a 5-year overall survival of approximately 50%. Early stage of the disease, small tumor size, previous hysterectomy, high pretreatment/treatment hemoglobin levels, and patients' age were correlated with a better clinical outcome. A brachytherapy boost should be delivered, especially in patients with higher-stage disease. The addition of concurrent weekly cisplatin should be considered in most patients, and transfusion should be used to maintain high hemoglobin levels.

68Ga-PSMA-11 PET/CT in prostate cancer patients with biochemical recurrence after radical prostatectomy and PSA <0.5 ng/ml. Efficacy and impact on treatment strategy.

PURPOSE: The primary aim of this retrospective, single-centre analysis was to assess the performance of 68Ga-PSMA-11 PET/CT in prostate cancer (PCa) patients in early PSA failure after radical prostatectomy (RP). The secondary aim was to assess the potential impact of 68Ga-PSMA-11 PET/CT on treatment strategy. METHODS: 68Ga-PSMA-11 PET/CT is performed in our institution within an investigational new drug (IND) trial in PCa patients with biochemical recurrence (BCR). The records of all patients enrolled between March 2016 and July 2017 were evaluated. These records were retrospectively analysed according to the following inclusion criteria: (a) RP as primary therapy, (b) proven BCR, ©) PSA levels in the range 0.2-0.5 ng/ml at the time of the 68Ga-PSMA-11 PET/CT investigation, and (d) no salvage radiotherapy (S-RT) performed after recurrence. The performance of 68Ga-PSMA-11 PET/CT was evaluated in terms of detection rate on a per-patient and a per-region basis (local vs. distant lesions). We further performed an intention-to-treat (ITT) analysis. The patient cohort was grouped into three subpopulations, blinded to the 68Ga-PSMA-11 PET/CT results, according to the patients' characteristics and different patterns of treatment: (1) S-RT (with or without systemic treatment), (2) stereotactic body radiotherapy (SBRT) (with or without systemic treatment), and (3) systemic treatment. The treatment strategy was re-evaluated for each patient taking into consideration the 68Ga-PSMA-11 PET/CT images. RESULTS: We enrolled 119 PCa patients (mean age 66 years, range 44-78 years) with a mean PSA level at the time of 68Ga-PSMA-11 PET/CT of 0.34 ng/ml (median 0.32 ng/ml, SD ±0.09, range 0.20-0.50 ng/ml). 68Ga-PSMA-1 1 PET/CT was positive in 41 of the 119 patients, resulting in an overall detection rate of 34.4%. 68Ga-PSMA-11 uptake was observed in the prostate bed (3 patients, 2.5%), in the pelvic lymph nodes (21, 17.6%), in the retroperitoneal lymph nodes (4, 3.4%) and in the skeleton (21, 17.6%). Regarding ITT, 81 patients (68.1%) were considered possible candidates for S-RT only in the prostate bed and none of the patients (0%) for SBRT. According to the 68Ga-PSMA-11 PET/CT results, the intended treatment was changed in 36 patients (30.2%). According to the PET/CT results, S-RT was recommended in 70 patients (58.8%), only to the prostate bed in 58 (48.7%) and SBRT in 29 (24.4%). The intended RT planning was modified in 36 (87.8%) of 41 patients with a positive 68Ga-PSMA-11 PET/CT result. CONCLUSION: In our patient series with PSA levels <0.5 ng/ml, 68Ga-PSMA-11 PET/CT had a detection rate of 34.4%. In the ITT analysis, 30.2% of patients had a change in the intended treatment. These data support the hypothesis that 68Ga-PSMA-11 PET/CT is a useful procedure in the management of PCa patients showing early recurrence after RP, and should be implemented in routine clinical practice.

Adjuvant chemoradiation in pancreatic cancer: impact of radiotherapy dose on survival.

BACKGROUND: To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). METHODS: A multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. RESULTS: Median follow-up was 35 months (range: 3-120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3-4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3-4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. CONCLUSIONS: Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.

Epid-based in vivo dose verification for lung stereotactic treatments delivered with multiple breath-hold segmented volumetric modulated arc therapy.

We evaluated an EPID-based in-vivo dosimetry (IVD) method for the dose verification and the treatment reproducibility of lung SBRT-VMAT treatments in clinical routine. Ten patients with lung metastases treated with Elekta VMAT technique were enrolled. All patients were irradiated in five consecutive fractions, with total doses of 50 Gy. Set-up was carried out with the Elekta stereotactic body frame. Eight patients were simulated and treated using the Active Breath Control (ABC) system, a spirometer enabling patients to maintain a breath-hold at a predetermined lung volume. Two patients were simulated and treated in free-breathing using an abdominal compressor. IVD was performed using the SOFTDISO software. IVD tests were evaluated by means of (a) ratio R between daily in-vivo isocenter dose and planned dose and (b) γ-analysis between EPID integral portal images in terms of percentage of points with γ-value smaller than one (γ% ) and mean γ-values (γmean ) using a 3%(global)/3 mm criteria. Alert criteria of ±5% for R ratio, γ%  < 90%, and γmean  > 0.67 were chosen. 50 transit EPID images were acquired. For the patients treated with ABC spirometer, the results reported a high level of accuracy in dose delivery with 100% of tests within ±5%. The γ-analysis showed a mean value of γmean equal to 0.21 (range: 0.04-0.56) and a mean γ% equal to 96.9 (range: 78-100). Relevant discrepancies were observed only for the two patients treated without ABC, mainly due to a blurring dose effect due to residual respiratory motion. Our method provided a fast and accurate procedure in clinical routine for verifying delivered dose as well as for detecting errors.

Hibernation and Radioprotection: Gene Expression in the Liver and Testicle of Rats Irradiated under Synthetic Torpor.

Hibernation has been proposed as a tool for human space travel. In recent years, a procedure to induce a metabolic state known as "synthetic torpor" in non-hibernating mammals was successfully developed. Synthetic torpor may not only be an efficient method to spare resources and reduce psychological problems in long-term exploratory-class missions, but may also represent a countermeasure against cosmic rays. Here we show the preliminary results from an experiment in rats exposed to ionizing radiation in normothermic conditions or synthetic torpor. Animals were irradiated with 3 Gy X-rays and organs were collected 4 h after exposure. Histological analysis of liver and testicle showed a reduced toxicity in animals irradiated in torpor compared to controls irradiated at normal temperature and metabolic activity. The expression of ataxia telangiectasia mutated (ATM) in the liver was significantly downregulated in the group of animal in synthetic torpor. In the testicle, more genes involved in the DNA damage signaling were downregulated during synthetic torpor. These data show for the first time that synthetic torpor is a radioprotector in non-hibernators, similarly to natural torpor in hibernating animals. Synthetic torpor can be an effective strategy to protect humans during long term space exploration of the solar system.

Treatment planning for spinal radiosurgery : A competitive multiplatform benchmark challenge.

PURPOSE: To investigate the quality of treatment plans of spinal radiosurgery derived from different planning and delivery systems. The comparisons include robotic delivery and intensity modulated arc therapy (IMAT) approaches. Multiple centers with equal systems were used to reduce a bias based on individual's planning abilities. The study used a series of three complex spine lesions to maximize the difference in plan quality among the various approaches. METHODS: Internationally recognized experts in the field of treatment planning and spinal radiosurgery from 12 centers with various treatment planning systems participated. For a complex spinal lesion, the results were compared against a previously published benchmark plan derived for CyberKnife radiosurgery (CKRS) using circular cones only. For two additional cases, one with multiple small lesions infiltrating three vertebrae and a single vertebra lesion treated with integrated boost, the results were compared against a benchmark plan generated using a best practice guideline for CKRS. All plans were rated based on a previously established ranking system. RESULTS: All 12 centers could reach equality (n = 4) or outperform (n = 8) the benchmark plan. For the multiple lesions and the single vertebra lesion plan only 5 and 3 of the 12 centers, respectively, reached equality or outperformed the best practice benchmark plan. However, the absolute differences in target and critical structure dosimetry were small and strongly planner-dependent rather than system-dependent. Overall, gantry-based IMAT with simple planning techniques (two coplanar arcs) produced faster treatments and significantly outperformed static gantry intensity modulated radiation therapy (IMRT) and multileaf collimator (MLC) or non-MLC CKRS treatment plan quality regardless of the system (mean rank out of 4 was 1.2 vs. 3.1, p = 0.002). CONCLUSIONS: High plan quality for complex spinal radiosurgery was achieved among all systems and all participating centers in this planning challenge. This study concludes that simple IMAT techniques can generate significantly better plan quality compared to previous established CKRS benchmarks.

Electrochemotherapy pre-treatment in primary squamous vulvar cancer. Our preliminary experience.

BACKGROUND AND OBJECTIVES: Previous studies showed a local tumor control of 80% in patients with relapsed squamous cell vulvar cancer (V-SCC) treated with electrochemotherapy. These results encouraged electrochemotherapy use as neo-adjuvant treatment in V-SCC. The objective of this study was to evaluate the effectiveness of electrochemotherapy in reducing tumor burden in V-SCC. METHODS: Patients with histological diagnosis of primary V-SCC eligible for surgery were enrolled. Following accurate mapping of all the lesions, electrochemotherapy was performed. One month after electrochemotherapy clinical response was evaluated according to RECIST criteria and the type of surgery was confirmed or modified. Adjuvant therapies were prescribed depending on stage and pathological evaluation. RESULTS: We report the results from nine patients treated with electrochemotherapy before surgery. The median age was 64 years (range 51-81 years). Tumor response after electrochemotherapy was observed in seven patients (77.8%) with one CR and six PR, without complications. Tumor downsizing led to more conservative surgery in six patients (66.7%). At a median follow-up of 8 months (range 2-32 months) all patients were alive without disease. CONCLUSIONS: Our preliminary analysis suggests that ECT is a suitable treatment in patients with V-SCC before surgery, reducing the tumor size and the surgical resection.

Partially ablative radiotherapy (PAR) for large mass tumors using simultaneous integrated boost: A dose-escalation feasibility study.

PURPOSE: This study aimed to assess the feasibility to plan and deliver highly heterogeneous doses to symptomatic large tumors using volumetric modulated arc therapy (VMAT) and simultaneous integrated boost (SIB) during a short course palliative accelerated radiotherapy. METHODS: A patient with a large symptomatic chordoma infiltrating the right gluteal region was selected. A modified SIB treatment was implemented to irradiate the central volume of the tumor (boost target volume, BTV) up to 10 Gy/fraction in a dose escalation trial while maintaining the remaining tumor volume (planning target volume, PTV) and the surrounding healthy tissues within 5 Gy/fraction in twice daily fractions for two consecutive days. Four SIB plans were generated in the dual-arc modality; a basal dose of 20 Gy was prescribed to the PTV, while the BTV was boosted up to 40 Gy. For comparison purposes, plans obtained with a sequential boost (SEQ plans) were also generated. All plans were optimized to deliver at least 95% of the prescription dose to the targets. Dose contrast index (DCI), conformity index (CI), integral dose (ID), and the irradiated body volumes at 5, 10, and 20 Gy were evaluated. RESULTS: At equal targets coverage, SIB plans provided major improvement in DCI, CI, and ID with respect to SEQ plans. When BTV dose escalated up to 200% of PTV prescription, DCI resulted in 66% for SIB plans and 37% for SEQ plans; the ID increase was only 11% for SIB plans (vs 27% for SEQ plans) and the increase in healthy tissues receiving more than 5, 10, and 20 Gy was less than 2%. Pretreatment dose verification reported a γ-value passing rate greater than 95% with 3%(global)-2 mm. CONCLUSION: A modified SIB technique is dosimetrically feasible for large tumors, where doses higher than the tolerance dose of healthy tissues are necessary to increase the therapeutic gain.