Stereotactic ablative radiotherapy for unresectable inferior vena cava tumor thrombus in a patient with renal cell carcinoma: a case report.

PURPOSE: Treatment options for renal cell carcinoma (RCC) with inferior vena cava tumor thrombus (IVC-TT) are limited and carry substantial risks. Currently, there are no standard treatment options in the setting of recurrent or unresectable RCC with IVC-TT. METHODS: We report our experience of treating an IVC-TT RCC patient with stereotactic body radiation therapy (SBRT). RESULTS: This 62-year-old gentleman presented renal cell carcinoma with IVC-TT and liver metastases. Initial treatment consisted of radical nephrectomy and thrombectomy followed by continuous sunitinib. At 3 months, he developed an unresectable IVC-TT recurrence. A fiducial marker was implanted into the IVC-TT by catheterization. New biopsies were performed at the same time, demonstrating a recurrence of the RCC. SBRT consisted of 5 fractions of 7 Gy to the IVC-TT with excellent initial tolerance. He subsequently received anti-PD1 therapy (nivolumab). At 4 years follow-up, he is doing well with no IVC-TT recurrence and no late toxicity. CONCLUSION: SBRT appears to be a feasible and safe treatment for IVC-TT secondary to RCC in patients who are not candidates for surgery.

French-style genetics v. 2.0: The "e-CohortE" project.

In the digital age, a genetics cohort has become much more than a simple means of determining the cause of a disease. Two-sided markets, of which 23andMe, Ancestry DNA and MyHeritage are the best known, have showed this perfectly over the last few years: a cohort has become a means of producing massive amounts of data for medical, scientific and commercial exploitation, and for genetic use in particular. French law does not currently allow these foreign private companies to develop on French national territory and also forbids the creation of similar entities in France. However, at least in theory, this same law does not preclude the creation of new types of cohorts in France inspired by the success of two-sided markets but retaining features specific to the French healthcare management system. We propose an optimal solution for France, for genomic studies associated with multi-subject questionnaires, still purely theoretical for the moment: the development, with no need for any change in the law, of France's own version of "Genetics v.2.0": "e-CohortE."

Parameter identification of a model for prostate cancer treated by intermittent therapy.

Adenocarcinoma is the most frequent cancer affecting the prostate walnut-size gland in the male reproductive system. Such cancer may have a very slow progression or may be associated with a "dark prognosis" when tumor cells are spreading very quickly. Prostate cancers have the particular properties to be marked by the level of prostate specific antigen (PSA) in blood which allows to follow its evolution. At least in its first phase, prostate adenocarcinoma is most often hormone-dependent and, consequently, hormone therapy is a possible treatment. Since few years, hormone therapy started to be provided intermittently for improving patient's quality of life. Today, durations of on- and off-treatment periods are still chosen empirically, most likely explaining why there is no clear benefit from the survival point of view. We therefore developed a model for describing the interaction between the tumor environment, the PSA produced by hormone-dependent and hormone-independent tumor cells, respectively, and the level of androgens. Model parameters were identified using a genetic algorithm applied to the PSA time series measured in a few patients who initially received prostatectomy and were then treated by intermittent hormone therapy (LHRH analogs and anti-androgen). The measured PSA time series is quite correctly reproduced by free runs over the whole follow-up. Model parameter values allow for distinguishing different types of patient (age and Gleason score) meaning that the model can be individualized. We thus showed that the long-term evolution of the cancer can be affected by durations of on- and off-treatment periods.

Biosimilar filgrastim treatment patterns and prevention of febrile neutropenia: a prospective multicentre study in France in patients with solid tumours (the ZOHé study).

BACKGROUND: The ZOHé study was a prospective, non-interventional, multicentre study in France to assess the use of biosimilar filgrastim Zarzio® (Sandoz filgrastim) in routine clinical practice in patients at risk of neutropenia-inducing chemotherapy (CT). METHODS: Patients ≥ 18 years undergoing CT for a malignant disease and with a first prescription for Zarzio® were enrolled in two cohorts according to tumour type: solid tumour or haematological malignancy; results from the solid tumour cohort are reported here. Analyses primarily described the prescription and use of Zarzio® in current practice, and also included identification of factors linked to prescription for primary prophylaxis and comparison of Zarzio® use in relation to European Organisation for Research and Treatment of Cancer (EORTC) guidelines. RESULTS: Responses were obtained from 125 physicians and 1179 patients with solid tumours, allowing robust statistical analysis of the data. Use of Zarzio® in clinical practice was relatively standardised and followed label indication. The patient profile was in line with EORTC guidelines for granulocyte colony-stimulating factor (G-CSF) febrile neutropenia (FN) prophylaxis, and the majority of patients had ≥ 1 EORTC factor(s) for increased risk of febrile neutropenia. Some patients (10.8%) received Zarzio® despite receiving CT regimens categorised in guidelines as low (< 10%) FN risk ('over prophylaxis'). Nearly half of patients' CT regimens did not have a recommended FN risk category. Zarzio® was commonly initiated as primary prophylaxis; initiation in Cycle ≥ 2 of the current line of CT was associated more with a history of neutropenia. The safety profile of Zarzio® was confirmed. CONCLUSIONS: Use of Zarzio® in routine clinical practice is generally in line with EORTC guidelines for prophylaxis of CT-induced neutropenia. Patient-related risk factors appear to be a stronger driver of clinicians' decision to initiate Zarzio® than CT risk category for FN. The intrinsic risk of FN associated with a specific CT protocol is often miscategorised by physicians. In contrast to earlier reports of underuse of G-CSF prophylaxis, over prophylaxis is observed in a small subgroup of patients with FN risk of < 10%.

Early onset breast cancer: differences in risk factors, tumor phenotype, and genotype between North African and South European women.

PURPOSE: This report compares the risk factors, the tumor phenotypes, and the BRCA1/BRCA2 genotype of early onset breast cancer (EOBC) patients between Southern Europe and North Africa. METHODS: Four hundred and fifty six women with invasive EOBC (≤40 years) were prospectively included from four centers in France (n = 270) and four centers in North Africa (Algeria, Egypt, Morocco, Tunisia; n = 186). Life style, tumor phenotype, familial history, BRCA1/BRCA2 genotype were compared between the two populations. RESULTS: We found an older age at menarche, a higher number of childbearing, a more frequent breastfeeding, a higher body mass index, a lower use of oral contraceptives in North African women compared to French women. TNM stage at diagnosis was higher in North African women than in French women. North African women had a lower incidence of triple negative and proliferative (Ki 67 index > 20%) tumors. There was a lower rate of BRCA1 mutation in North Africa (7 vs. 15%, P = 0.02). Three putative BRCA1/2 founder mutations were identified in North Africa. CONCLUSIONS: In EOBC, we found significant differences in risk factors, phenotype and a higher incidence of BRCA1 mutations in Southern Europe as compared to North Africa. The worst prognosis previously reported for EOBC in North Africa is more likely due to a higher stage at diagnosis than to a more aggressive phenotype, since triple negative tumors are more common in Southern Europe and advanced tumors in North Africa.

Use of iron sucrose and red blood cell transfusions in anaemic cancer patients in France (OncoFer study).

PURPOSE: This report describes the results of an observational, retrospective cohort study, evaluating the use of iron sucrose (IS) and red blood cell (RBC) transfusions in patients with cancer in routine clinical practice in France. A parallel investigated cohort treated with ferric carboxymaltose (FCM) has been reported earlier. METHODS: Data of patients with a solid tumour or haematological malignancy who have received IS or an RBC transfusion during 2010 from 3 months prior (M-3) to 3 months post first treatment (M+3) were analysed. RESULTS: Data from 46 patients who had received IS (400 mg median total iron dose) and 357 patients who had received RBC transfusions as first treatment (baseline) were included. Median haemoglobin levels improved from 9.9 g/dL (interquartile range 9.2; 11.0 g/dL) at baseline to 12.4 g/dL (11.4; 13.1 g/dL) at M+3 in IS-treated patients and from 8.2 g/dL (7.8; 8.8 g/dL) at baseline to 10.1 g/dL (8.8; 11.1 g/dL) in transfused patients. An erythropoiesis-stimulating agent was given to 54.3 and 28.9% of patients in the IS and the RBC transfusion groups, respectively, resulting in slightly better mean haemoglobin increase in both groups (2.4 vs 1.5 g/dL and 2.0 vs 1.6 g/dL, respectively). No severe nor serious adverse reaction and no hypersensitivity reactions were reported. CONCLUSION: Both IS and RBC transfusions effectively increased Hb levels in patients with cancer. IS was safe and well tolerated in this population. Considering prior reported results with FCM, using FCM may reduce ESA dose requirements and the required number of infusions.

Clinical use of ferric carboxymaltose in patients with solid tumours or haematological malignancies in France.

PURPOSE: This study collected data on the use of ferric carboxymaltose (FCM) in a cancer patient population in France to evaluate the feasibility and the conditions of use of FCM in routine clinical practice beyond the limiting criteria of clinical trials. METHODS: This observational, prospective study of patients with a solid tumour or a haematological malignancy who have received treatment with FCM after 01 July 2011 evaluated data about the circumstances of iron administration, concomitant medication and laboratory tests in the period from 3 months prior to the first FCM administration (baseline) until 3 months post-baseline. RESULTS: Data from 367 FCM-treated patients were analysed. FCM was mainly given as a single dose at baseline (69.2%) and without additional erythropoiesis-stimulating agent (ESA, 64.3%). The median total iron dose was 1000 mg per patient. Median haemoglobin (Hb) levels of FCM-treated patients improved from 10.3 g/dL (interquartile range 9.5, 11.1 g/dL) at baseline to 11.8 g/dL (11.1, 13.0 g/dL) until the end of the 3-month observational period. Patients treated with FCM alone or additional ESA achieved similar median Hb increase (1.3 [0.4, 2.1] g/dL and 1.4 [0.4, 2.5] g/dL, respectively). Patients with baseline Hb up to 11.0 g/dL and serum ferritin up to 500 ng/mL and beyond achieved stable median Hb levels ≥11.0 g/dL without signs of iron overload. No severe or serious adverse reaction and no hypersensitivity reactions were reported. CONCLUSIONS: The results of this observational study confirm the effectiveness and tolerability of FCM when given in clinical routine practice alone or in combination with an ESA.

Comparison between two different algorithms used for pretreatment QA via aSi portal images.

Several algorithms exist to perform quality assurance for volumetric-modulated arc therapy (VMAT) treatments based on electronic portal imaging devices (EPID). These algorithms are used to compare doses (convert into water, GLAaS) and fluences (in amorphous silicon (aSi), Varian portal dosimetry). The aim of this study is to compare the two methods using clinical data. In this study, Varian portal dosimetry (VPD) and Epiqa solutions were compared. We used a same set of patient images data treated with 6 MV and 20 MV photon energies and different locations. The response of the portal imaging device was also investigated with different field sizes, monitor units, dose rates, sag effect, and linac daily output. All images were acquired on an electronic portal imaging device (EPID) positioned at source detector distance (SDD) of 100 cm. A virtual water phantom was used for Epiqa to calculate the dose matrices at the maximum depth doses dmax. The 2D gamma evaluation index (GAI) was performed to quantitatively compare the results given by the two solutions. The response of the EPID gave a good agreement with Epiqa (deviation less than 1%) for MU greater than 20 for both 6 MV and 20 MV photon energies. For VPD, the upward sloping trend showed a good agreement for MU higher than 50. Dose rate evaluations for both methods gave a deviation of, respectively, 0.4 and 0.5 % for 6 MV and 20 MV. The gamma criteria of 3 mm for distance to agreement and 3 % for dose difference was, as mean ± 1SD, 99.81% ± 1.48% and 99.42% ± 0.97% for VPD and Epiqa, respectively, for 6 MV photon energy. The mean values of the gamma criteria for the collected data using 20 MV photon energy were, respectively, 98.33% ± 2.41% and 98.12% ± 1.99% for VPD and Epiqa. The output constancy deviation correction (a 10 × 10cm² reference field plan to obtain absorbed dose despite the linac monitor daily variations) showed a mean deviation of, respectively, 0.07% ± 0.57% and 0.16% ± 1.38% for 6 MV and 20 MV photon energies. For sag effect, a slight improvement was noticed for realignment of the integrated image and was 0.25%± 0.69% for 6 MV and 0.40% ± 0.57% for 20 MV. The clinical data were used for pretreatment QA with the two systems, both VPD and Epiqa software, showed acceptable and similar results for low and high energies. Furthermore, Epiqa shows better linearity response for low MU.

French national survey on breast cancer care: caregiver and patient views.

PURPOSE: To improve the quality of care for patients with breast cancer, an analysis of the health-care pathway, considering feedback from both health-care practitioners (HCPs) and patients, is needed. METHODS: Between 2020 and 2022, we conducted a survey at French breast cancer centers and analyzed information from questionnaires completed by HCPs and patients. We collected information on center organization, diagnostic processes, treatment decisions and modalities, supportive care, patient advocacy groups, and work issues. RESULTS: Twenty-three breast cancer centers were included and questionnaires completed by 247 HCPs and 249 patients were analyzed. The centers closely followed the legal French framework for cancer treatments, which includes formal diagnostic announcements, multidisciplinary tumor boards, personalized treatment summaries, and supportive care access. HCPs and patients were satisfied with the time to diagnosis (≤ 2 weeks as evaluated by 75% of patients), time to surgery (mean 61 days), time between surgery and chemotherapy (mean 47 days), and time between surgery and radiotherapy (mean 81 days). Fertility preservation counseling for women under 40 years of age was systematically offered by 67% of the HCPs. The majority (67%) of the patients indicated that they had received a personalized treatment summary; the topics discussed included treatments (92%), tumor characteristics (84%), care pathways (79%), supportive care (52%), and breast reconstruction (33%). Among HCPs, 44% stated that reconstructive surgery was offered to all eligible patients and 57% and 45% indicated coordination between centers and primary care physicians for adverse effects management and access to supportive care should be improved, for chemotherapy and radiotherapy, respectively. Regarding patient advocacy groups, 34% of HCPs did not know whether patients had contact and only 23% of patients declared that they had such contact. For one-third of working patients, work issues were not discussed. Twenty-eight percent of patients claimed that they had faced difficulties for supportive care access. Among HCPs, 13% stated that a formal personalized survivorship treatment program was administered to almost all patients and 37% almost never introduced the program to their patients. Compliance to oral treatments was considered very good for 75-100% of patients by 62% of HCPs. CONCLUSIONS: This study provides an updated analysis of breast cancer care pathways in France. Overall, the initial processes of diagnosis, announcement, and treatment were swift and were in agreement with the best care standards. No barriers to accessing care were identified. Based on the study findings, we proposed several strategies to improve the quality of care for patients in supportive care, coordination with primary care physicians, reconstructive surgery, and fertility preservation access.

Depression is associated with some patient-perceived cosmetic changes, but not with radiotherapy-induced late toxicity, in long-term breast cancer survivors.

OBJECTIVE: Although depression is prevalent in long-term breast cancer survivors (LTBCS; ≥ 5 years since diagnosis), it is underdiagnosed and undertreated. A better understanding of factors associated with depression could improve depression screening, treatment, and prevention in this population. Our study aimed to assess the link between patient and doctor ratings of breast cosmetic outcomes, late radiotherapy toxicity, and depression in LTBCS. METHODS: In all, 214 patients recruited from the ARCOSEIN study were assessed for late radiotherapy toxicity (by using the LENT-SOMA scale) and patient and doctor ratings of breast cosmetic outcomes (mean = 6.7 years since the end of treatment). We reassessed 120 of these patients for depression (HAD) during a second wave of long-term assessment (mean = 8.1 years since the end of treatment). We used univariate analyses and polytomous logistic regression analyses to predict the HAD depression, which was defined as follows: normal, 0-7 points; and significant depression, ≥ 8 points (8-10 points, possible depression; ≥ 11 points, probable depression). RESULTS: The mean HAD depression score was 4.5 ± 3.6. 19. 2% of our population had significant depression, 6.7% with probable depression, and 12.5% with possible depression. Significant depression was not associated with late radiotherapy toxicity or initial cancer-related variables. Patients with probable depression reported worse cosmetic outcomes than nondepressed patients in terms of perceived breast largeness (p = 0.04), breast deformation (p = 0.02), and changes in skin pigmentation (p = 0.03). CONCLUSIONS: In LTBCS, depression seems to be more strongly associated with changes in some patients' perceived breast cosmetic outcome than late treatment toxicity or initial cancer-related variables.

Gene expression profiling of peripheral blood mononuclear cells from women with cervical lesions reveals new markers of cancer.

Cervical cancer (CC) is a multifactorial disease of which human papillomavirus (HPV) is the main etiological agent. Despite cervical Pap smear screening and anti­HPV vaccination, CC remains a major public health issue. Identification of specific gene expression signatures in the blood could allow better insight into the immune response of CC and could provide valuable information for the development of novel biomarkers. The present study performed a transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from Senegalese patients with CC (n=31), low­grade cervical intraepithelial neoplasia (CIN1; n=27) and from healthy control (CTR) subjects (n=29). Individuals in the CIN1 and CTR groups exhibited similar patterns in gene expression. A total of 182 genes were revealed to be differentially expressed in patients with CC compared with individuals in the CIN1 and CTR groups. The IL1R2, IL18R1, MMP9 and FKBP5 genes were the most upregulated, whereas the T­cell receptor α gene TRA was the most downregulated in the CC group compared with in the CIN1 and CTR groups. The pathway enrichment analysis of the differentially expressed genes revealed pathways directly and indirectly linked to inflammation. To the best of our knowledge, the present study is the first large transcriptomic study on CC performed using PBMCs from African women; the results revealed the involvement of genes and pathways related to inflammation, most notably the IL­1 pathway, and the involvement of downregulation of the T­cell receptor α, a key component of the immune response. Several of the stated genes have already been reported in other cancer studies as putative blood biomarkers, thus reinforcing the requirement for deeper investigation. These findings may aid in the development of innovative clinical biomarkers for CC prevention and should be further replicated in other populations.

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study.

BACKGROUND: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. OBJECTIVE: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. DESIGN, SETTING, AND PARTICIPANTS: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. RESULTS AND LIMITATIONS: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). CONCLUSIONS: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. PATIENT SUMMARY: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer.

Robot-Assisted Surgery vs Robotic Stereotactic Body Radiotherapy in Prostate Cancer: A Cost-Utility Analysis.

Prostate cancer is the most common men cancer in France. Continuous progress in oncology led to develop robot-assisted Radical Prostatectomies (rRP) and robot-assisted stereotactic body radiotherapy (rSBRT). The present study aims at comparing economic and clinical impacts of prostate cancer treatments performed either with rSBRT or rRP in France. A Markov model using TreeAge Pro software was chosen to calculate annual costs; utilities and transition probabilities of localized prostate cancer treatments. Patients were eligible for radiotherapy or surgery and the therapeutic decision was a robot-assisted intervention. Over a 10-year period, rSBRT yielded a significantly higher number of quality-adjusted life years than rRP (8.37 vs 6.85). In France, rSBRT seemed more expensive than rRP (€19,475 vs €18,968, respectively). From a societal perspective, rRP was more cost-saving (incremental cost effectiveness ratio = €332/QALY). The model was sensitive to variations of costs of the initial and recurrence state in one-way sensitivity analyses. Robot-assisted stereotactic body radiotherapy seems more cost-effective than Radical Prostatectomy in terms of QALY despite the slightly higher initial cost due to the use of radiotherapy. It would be interesting to conduct comparative quality of life studies in France over longer periods of time.

Sleep Disorders and Quality of Life in Patients With Cancer: Prospective Observational Study of the Rafael Institute.

BACKGROUND: Sleep disorders are a common occurrence in the general population. Yet today, it is clearly agreed that sleep disorders represent both a cancer risk factor and a biological consequence of the of the activation of the immuno-inflammatory system induced by cancer itself. OBJECTIVE: The aim of this study was to assess the impact of sleep disorders on quality of life and identify the type of disorder and its causes in order to offer an adapted and personalized care plan. METHODS: In a survey completed during the COVID-19 lockdown, 2000 hours of interviews were collected by remote consultations. During these calls, we administered a sleep questionnaire. This questionnaire was inspired by the STOP-BANG questionnaire and enquired about 6 items. The demographic details of each patient (eg, age and sex), the nature of the pathology, their past treatments, the ongoing cancer treatment, the mood, whether or not the patient is anxious or depressed, and the use of sleeping drug pills were analyzed. A univariate analysis was performed according to the presence or absence of fatigue. Chi-square test was applied to assess possible differences of variables' link to sleep disturbance between patients complaining of fatigue and those without fatigue. The same test was then used to analyze patients on hormone therapy and those with no hormone therapy for 2 types of cancer-breast cancer and prostate cancer. RESULTS: A total of 905 patients were prospectively included in this study. The average age was 66.7 (5 SD) years, and 606 (67%) patients were women; 142 patients declared being overweight. Breast cancer was the most frequently reported cancer. Nocturnal awakening was reported by 70% (n=633), fatigue by 50% (n=452), difficulty falling asleep by 38% (n=343), snoring reported by an independent observer in 38% (n=343), and apnea reported by an independent observer in 9% (n=81) of the patients. The univariate analysis showed that the feeling of tiredness was significantly greater in patients reporting difficulty falling asleep (P≥.99), pain (P<.001), and frequent awakening (P<.001), as well as in patients who were not receiving cancer treatment (P<.001). The univariate analysis showed that patients who were receiving breast cancer treatment and were under hormone therapy reported difficulty falling asleep (P=.04) and pain (P=.05). In a univariate analysis of patients treated for prostate cancer, being overweight was the only factor reported that had a statistically significant value. CONCLUSIONS: Our preliminary data support and are consistent with data in the literature regarding the importance of sleep disorders in oncology. This justifies the usefulness of a diagnosis and early treatment of sleep disorders in patients with cancer. The Rafael Institute sleep observatory will enable patients to be identified and treated.

Stereotactic Re-Irradiation for Local Recurrence after Radical Prostatectomy and Radiation Therapy: A Retrospective Multicenter Study.

Prostate cancer recurrence in patients previously treated with radical prostatectomy and radiation therapy is challenging. Re-irradiation could be an option, but data regarding efficacy and safety are lacking. We retrospectively evaluated salvage re-irradiation for local recurrence after prostatectomy and external beam radiation therapy. We collected data from 48 patients who underwent salvage reirradiation with stereotactic radiation therapy for local prostate cancer recurrence in the prostatic bed at four French centers. Fifteen patients (31%) were on androgen deprivation therapy during stereotactic radiotherapy. Biochemical response and relapse-free survival were analyzed, and post-treatment toxicities were assessed according to the Common Terminology of Adverse Events criteria. Five patients had grade 3 late bladder toxicity (cystitis), three had grade 3 late incontinence, and one had grade 3 late chronic pain. At three months, 83% of patients had a positive biochemical response. The median follow-up was 22 months. At the end of the follow-up, 21 patients (43%) had a biochemical relapse. The median time to biologic relapse was 27 months. The biochemical relapse rates at 1 and 2 years were 80% and 52%, respectively. In conclusion, salvage re-irradiation for recurrent prostate cancer in the prostate bed may generate significant toxicity rates, and a prospective study with appropriate patient selection is needed to evaluate its effectiveness.

Integrative Oncology: An International Perspective from Six Countries.

In June 2019, a meeting was held in Paris in which experts from different countries (Israel, Spain, Belgium, Italy, USA, and France) met to discuss a selection of topics in integrative oncology (IO). The objectives were to draw on the delegates' experience and expertise to begin an international collaboration, sharing details of differing existing models and discussing future perspectives to help define and guide practice in IO and define unmet needs. This report presents a summary of the meeting's main presentations, and also reports on the experts' responses to a questionnaire examining different aspects of IO service delivery, infrastructure, and utilization.

No Association of Early-Onset Breast or Ovarian Cancer with Early-Onset Cancer in Relatives in BRCA1 or BRCA2 Mutation Families.

According to clinical guidelines, the occurrence of very early-onset breast cancer (VEO-BC) (diagnosed ≤ age 30 years) or VEO ovarian cancer (VEO-OC) (diagnosed ≤ age 40 years) in families with BRCA1 or BRCA2 mutation (BRCAm) prompts advancing the age of risk-reducing strategies in relatives. This study aimed to assess the relation between the occurrence of VEO-BC or VEO-OC in families with BRCAm and age at BC or OC diagnosis in relatives. We conducted a retrospective multicenter study of 448 consecutive families with BRCAm from 2003 to 2018. Mean age and 5-year-span distribution of age at BC or OC in relatives were compared in families with or without VEO-BC or VEO-OC. Conditional probability calculation and Cochran-Mantel-Haenszel chi-square tests were used to investigate early-onset cancer occurrence in relatives of VEO-BC and VEO-OC cases. Overall, 15% (19/245) of families with BRCA1m and 9% (19/203) with BRCA2m featured at least one case of VEO-BC; 8% (37/245) and 2% (2/203) featured at least one case of VEO-OC, respectively. The cumulative prevalence of VEO-BC was 5.1% (95% CI 3.6-6.6) and 2.5% (95% CI 1.4-3.6) for families with BRCA1m and BRCA2m, respectively. The distribution of age and mean age at BC diagnosis in relatives did not differ by occurrence of VEO-BC for families with BRCA1m or BRCA2m. Conditional probability calculations did not show an increase of early-onset BC in VEO-BC families with BRCA1m or BRCA2m. Conversely, the probability of VEO-BC was not increased in families with early-onset BC. VEO-BC or VEO-OC occurrence may not be related to young age at BC or OC onset in relatives in families with BRCAm. This finding-together with a relatively high VEO-BC risk for women with BRCAm-advocates for MRI breast screening from age 25 regardless of family history.

Salvage stereotactic body radiotherapy (SBRT) for intraprostatic relapse after prostate cancer radiotherapy: An ESTRO ACROP Delphi consensus.

BACKGROUND AND PURPOSE: Between 30% and 47% of patients treated with definitive radiotherapy (RT) for prostate cancer are at risk of intraprostatic recurrence during follow-up. Re-irradiation with stereotactic body RT (SBRT) is emerging as a feasible and safe therapeutic option. However, no consensus or guidelines exist on this topic. The purpose of this ESTRO ACROP project is to investigate expert opinion on salvage SBRT for intraprostatic relapse after RT. MATERIALS AND METHODS: A 40-item questionnaire on salvage SBRT was prepared by an internal committee and reviewed by a panel of leading radiation oncologists plus a urologist expert in prostate cancer. Following the procedure of a Delphi consensus, 3 rounds of questionnaires were sent to selected experts on prostate re-irradiation. RESULTS: Among the 33 contacted experts, 18 (54.5%) agreed to participate. At the end of the final round, participants were able to find consensus on 14 out of 40 questions (35% overall) and major agreement on 13 questions (32.5% overall). Specifically, the consensus was reached regarding some selection criteria (no age limit, ECOG 0-1, satisfactory urinary flow), diagnostic procedures (exclusion of metastatic disease, SBRT target defined on the MRI) and therapeutic approach (no need for concomitant ADT, consideration of the first RT dose, validity of Phoenix criteria for salvage SBRT failure). CONCLUSION: While awaiting the results of ongoing studies, our ESTRO ACROP Delphi consensus may serve as a practical guidance for salvage SBRT. Future research should address the existing disagreements on this promising approach.

Stereotactic prostate focal reirradiation therapy for local recurrence: preliminary results of Hartmann Oncology Radiotherapy Group.

OBJECTIVE: Our objective was to report our experience and to evaluate the feasibility and toxicity of focal salvage stereotactic body radiation therapy (SBRT) in patients with post-radiation local recurrence of prostate cancer. METHODS: We retrospectively reviewed medical records of patients treated with Cyberknife ® between October 2014 and April 2017 at our institution for a focal reirradiation delivered to the prostate/prostatic bed for local recurrence after radical or adjuvant radiotherapy. All patients underwent prostate biopsies at recurrence at the time of fiducial markers placement, had choline PET/CT and pelvic MRI. The treatment consisted in 36 Gy in six fractions delivered every other day. Post reirradiation toxicities were assessed according to the CTCAE v4 (Common Terminology Criteria for Adverse Events). RESULTS: 42 patients were treated with followed with a median follow-up of 21 months (range 3 - 31). 34 patients had biopsy proven recurrence. The initial treatment was radical prostatectomy and radiation therapy for 9 patients and radiation therapy alone for 33 patients. 23 patients from the group of prostate reirradiation had placement of rectal spacers. No Grade 4 or 5 toxicity were observed. 27 acute urinary events were recorded: 18 patients experienced Grade 1, 9 patients experienced Grade 2 toxicity and 1 patient experienced Grade 3 urinary toxicity, namely cystitis and/or dysuria. No Grade 2 or more digestive toxicity was observed. Rectal doses were significantly lower with rectal spacers. CONCLUSION: Salvage focal Cyberknife ® seems feasible and show promising results. ADVANCES IN KNOWLEDGE: SBRT for local prostate cancer recurrence after initial radiotherapy is well tolerated with short follow-up.

Safety and efficacy of fiducial marker implantation for robotic stereotactic body radiation therapy with fiducial tracking.

PURPOSE: The purpose of this study was to assess the feasibility, efficacy and toxicity of fiducial marker implantation and tracking in CyberKnife® stereotactic radiation therapy (SBRT) applied to extracranial locations. MATERIALS AND METHOD: This is a retrospective, single-centre, observational study to collect the data of all patients treated by stereotactic radiation therapy with fiducial marker tracking at extracranial locations, conducted between June 2014 and November 2017. Information regarding the implantation procedure, the types of toxicity related to marker implantation and the number of markers implanted/tracked during treatment were collected. Complication rates were evaluated using the CTCAE v4 [Common Terminology Criteria for Adverse Events] scale. The technical success rate was based on the ability to optimally track the tumor throughout all treatment fractions. RESULTS: Out of 2505 patients treated by stereotactic radiation therapy, 25% received treatment with fiducial marker tracking. The total number of implantation procedures was 616 and 1543 fiducial markers were implanted. The implantation-related complication rate was 3%, with 16 Grade 1 events and 4 Grade 2 events. The number of treated patients and the number of implanted markers has gradually increased since the technique was first implemented. The median treatment time was 27 min (range 10-76). 1295 fiducials were effectively tracked throughout all treatment fractions, corresponding to a technical success rate of 84%. The difference between the number of fiducials implanted and those tracked during treatment decreased significantly as the site's experience increased. CONCLUSION: Fiducial marker implantation and tracking is feasible, well-tolerated, and technically effective technique in SBRT for extracranial tumors.