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.

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.

Combined-modality treatment for locally advanced cervical cancer in a woman with Bloom-like syndrome: A case report and review of the literature.

We report the case of a 46-year-old woman with Bloom-like syndrome affected with locally advanced cervical cancer. She was treated with induction chemotherapy and radical radiation therapy concurrent with chemotherapy (carboplatin and paclitaxel). She was able to complete treatment, but grade III toxicities were observed. The limited relevant literature is presented. We conclude that the management of patients with DNA repair deficiency is challenging for the team in charge because of the potentially high sensitivity to treatment and the lack of clear recommendations in the literature. The main objective remains to deliver the optimal treatment while reducing toxicities.

Proton therapy for adult craniopharyngioma: Experience of a single institution in 91 consecutive patients.

BACKGROUND: Craniopharyngioma (CP) in adults is a rare benign tumor associated with many morbidities, with limited contemporary studies to define treatment, and follow-up guidelines. METHODS: A single-center retrospective study was conducted on patients aged ≥ 18 years from 2006-2018 with CP and who were treated with proton therapy (PT). Late toxicity was defined as a minimum of 18 months from diagnosis. Overall survival (OS), local recurrence-free survival (LRFS), and toxicity were characterized using Kaplan-Meier and Cox regression analyses. RESULTS: Ninety-one patients met the criteria, with a median age of 37 years (range 18-82 years). PT was conducted after tumor resection in 88 patients (97%), in 64 patients (70.3%) as an adjuvant strategy and in 27 (29.7%) after recurrent disease. Three patients received exclusive PT. A median MRI follow-up of 39 months revealed 35.2% complete response, 49.5% partial response, and 9.9% stable disease. Five patients developed local recurrence (LR). The pattern of failure study showed that these five LR were within the GTV volume. The 5-year LRFS was 92.0% [CI 95% 84.90-99.60]. All the patients were alive at the end of the follow-up. Patients requiring treatment adaptation during PT tend to have a higher risk of LR (P = .084). Endocrinopathy was the most frequent grade ≥ 2 late toxicity. Among patients who were symptom-free before the start of treatment, none developed hearing toxicity but four (9.8%) developed visual disorders and 10 (11.3%) symptomatic memory impairment. Patients with large tumors had a higher risk of developing symptomatic memory impairment (P = .029). CONCLUSION: Adults with CP treated with PT have favorable survival outcomes, with acceptable late toxicity. Prospective quality-of-life and neurocognitive studies are needed to define late adverse effects better.

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.

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.

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.

Proton Beam Therapy for Thymic Carcinoma with Pericardial Involvement.

PURPOSE: Thymic malignancies are the most common anterior mediastinal tumors. Advanced thymic carcinoma treatment relies on chemotherapy and definitive radiation therapy when possible. However, pericardial involvement is problematic for radiation therapy treatment planning owing to significant cardiac radiation exposure. We report the first case of definitive proton beam therapy (PBT) for an advanced thymic carcinoma with pericardial invasion. MATERIALS AND METHODS: We report the case of a 69-year-old patient treated with definitive radiation therapy for a stage IVB thymic carcinoma with pericardial invasion. Mean doses delivered to critical organs at risk were compared between deep inspiration breath-hold (DIBH) volumetric modulated arc therapy (VMAT) and DIBH-PBT. RESULTS: When compared to DIBH-VMAT, DIBH-PBT reduced the mean doses delivered to the heart by 3.72 Gy (19.0% dose reduction), to the right lung by 5.9 Gy (41.7% dose reduction), to the left lung by 3.63 Gy (19.0% dose reduction), and to the esophagus by 3.57 Gy (21.3% dose reduction). Despite an early mediastinal relapse after 3.0 months, our patient is still alive after a 14-month follow-up, without any radiation-induced cardiac adverse events and is undergoing pembrolizumab-based immunotherapy. CONCLUSION: Proton beam therapy is an option for definitive irradiation of thymic malignancies invading the pericardium; in this situation, PBT reduces doses to the heart and may help to reduce cardiotoxicity when compared with photon techniques.

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.

Salvage Stereotactic Body Radiation Therapy for Local Prostate Cancer Recurrence After Radiation Therapy: A Retrospective Multicenter Study of the GETUG.

PURPOSE: To assess the efficacy and safety of salvage stereotactic body radiation therapy (SBRT) in patients with biopsy-proven local prostate cancer recurrence after radiation therapy. METHODS AND MATERIALS: Between April 2010 and January 2017, 100 patients were included in 7 centers. Disease extension was assessed by pelvic multiparametric magnetic resonance imaging and choline positron emission tomography in 87% and 94% of patients, respectively. The median time interval between the 2 treatments was 7.5 years (range, 2-18). Median prostate-specific antigen at recurrence was 4.3 ng/mL (range, 2-38). Median SBRT dose was 36 Gy (range, 25-36.25) in 6 fractions (range, 5-6), every other day. Thirty-four percent of patients were treated by androgen deprivation therapy for a median duration of 12 months. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Median follow-up was 29.3 months (range, 4-91). Second biochemical recurrence-free survival rate at 3 years was 55% (95% confidence interval [CI], 42%-66%). The initial D'Amico group, time interval after first radiation therapy, and SBRT dose were prognostic factors of biochemical recurrence-free survival in multivariate analysis (P = .09, P = .025, P = .018, respectively). No patient developed acute gastrointestinal toxicity of grade >1; rates of acute genitourinary toxicity of grade 2 and 3 were 8% and 1%, respectively. The actuarial 3-year grade ≥2 genitourinary and gastrointestinal toxicity was 20.8% (95% CI, 13%-29%) and 1% (95% CI, 0.1%-5.1%), respectively. One patient presented with neuritis of grade 3. CONCLUSIONS: With a short follow-up, this study shows that salvage SBRT allows for encouraging control and acceptable toxicity. Further prospective studies are necessary to confirm these preliminary results and to determine late toxicity.

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.