Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes.

BACKGROUND: The rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30-47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re­I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re­I. MATERIALS AND METHODS: We retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re­I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0-2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent. RESULTS: From January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7-50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2­year progression free survival (PFS) was 100% and 81.5%, respectively, while 2­year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12-39 months. Re­I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia). CONCLUSION: Linac-based SBRT is a safe technique for performing Re­I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Prognostic factors, efficacy, and toxicity of involved-node stereotactic body radiation therapy for lymph node oligorecurrent prostate cancer : An investigation of 117 pelvic lymph nodes.

BACKGROUND: The optimal radiotherapy regimen is not yet defined in the setting of oligorecurrent prostate cancer (oligorPC). There is evidence of high variability in treatment protocols among different centers worldwide, and no international consensus guidelines on treatment volumes, radiation schedules, and techniques. The purpose of the present retrospective study is to evaluate the efficacy and safety of involved-pelvic-node stereotactic body radiotherapy (SBRT) for oligorPC. MATERIALS AND METHODS: Patients with pelvic node oligorPC following primary surgery, radical radiotherapy, or salvage radiotherapy for biochemical or local relapse of prostate cancer who underwent involved-node SBRT with biological effective dose (BED) > 100 Gy, with or without concurrent and adjuvant androgen deprivation therapy (ADT), were retrospectively evaluated. Biochemical progression-free survival (bPFS), distant progression-free survival (DPFS), overall survival (OS), possible prognostic factors, and toxicity outcomes were investigated. RESULTS: From November 2012 to December 2019, 74 patients fitted the selection criteria. A total of 117 lesions were treated. Median follow-up was 31 months (range 6-89). Concurrent ADT was administered in 58.1% of patients. The 1­year, 2­year, and 3­year DPFS was 77%, 37%, and 19%, respectively; the 1­year, 2­year, and 3­year OS was 98%, 98%, and 95%, respectively. The presence of a single target lesion was associated with a statistically significant impact on OS. No in-field recurrence occurred. Patients who reached early prostate-specific antigen (PSA) nadir (< 3 months after SBRT) had a lower 3­year survival (p = 0.004). The value of PSA nadir after SBRT and the time between primary treatment and SBRT had an impact on bPFS. Concomitant ADT was associated with improved DPFS. No acute or early late (> 6 months) genitourinary and gastrointestinal adverse events of any grade were reported, albeit with relatively short median follow-up. CONCLUSION: SBRT is a safe and effective treatment for oligorPC, with a 100% local control rate in our series. It is not possible to clearly assess the opportunity to postpone ADT prescription in patients with two or more nodal metastases. The number of secondary lesions, time-to-nadir PSA, PSA nadir value, and the time interval between primary treatment and SBRT were identified as prognostic factors. Future prospective randomized studies are desirable to better understand the still open questions regarding the oligorecurrent prostate cancer state.

Radiation-induced breast angiosarcoma: report of two patients after accelerated partial breast irradiation (APBI) and review of the literature.

BACKGROUND: Angiosarcoma may rarely complicate radiotherapy of breast cancer. This so-called radiation-induced angiosarcoma (RIAS) occurs in less than 0.3% of patients that underwent breast conservation surgeries, usually years after completion of radiotherapy. CASE PRESENTATION: we introduce two cases of invasive ductal carcinoma who underwent lumpectomy and accelerated partial breast irradiation (APBI) as an alternative protocol to whole breast irradiation (WBI). They received adjuvant partial breast radiotherapy on tumor cavity for a total dose of 38.5 Gy in 10 fractions in 5 days using 3D-external-beam RT. In both cases, RIAS occurred eight years after radiotherapy, in the sub-cicatricial area in one patient and outside the irradiated area in the other one. They both underwent radical surgery and chemotherapy was performed in one patient. DISCUSSION: The underlying mechanism for development of RIAS is not well known, but its incidence seems to be increasing. RIAS after partial breast irradiation is very rare and has been reported in two cases so far. As it may be suggested in case 2, it is still a matter of debate if the risk of radiation-induced sarcoma is radiation-dose dependent. Although mastectomy is considered as a standard treatment, choice of treatment should be made according to the patient's specifications. CONCLUSION: There are very few studies in the literature that report RIAS after APBI. Present study is the only one reporting two cases after the external 3D technique APBI. Prognosis of RIAS remains poor. Only a careful evaluation in a multidisciplinary context can offer to the patients the best result in terms of local control and survival.

Adjuvant intraoperative radiotherapy for selected breast cancers in previously irradiated women: Evidence for excellent feasibility and favorable outcomes.

BACKGROUND: The present report provides preliminary outcomes with intraoperative radiotherapy delivered to women with breast cancer included in a re-irradiation program. MATERIALS AND METHODS: From October 2010 to April 2014, thirty women were included in a re-irradiation protocol by exploiting IORT technique. The median time between the two irradiations was 10 years (range 3-50). All patients underwent conservative surgery, sentinel lymph node excision and IORT with electron beam delivered by a mobile linear accelerator. Primary endpoint was esthetic result and consequential/late toxicity; secondary endpoints were local control (LC), disease free survival (DFS) and overall survival (OS). RESULTS: With a median follow up of 47 months (range 10-78), we analyzed 29 patients (1 lost at follow up). Twenty-seven patients (90%) had presented breast cancer local relapse or a new primary cancer in the same breast after a previous conservative surgery plus radiation treatment; three patients (10%) had previously received irradiation with mantle field for Hodgkin Lymphoma. Esthetic result was excellent in 3 pts (10%), good in 12 pts (41%), fair in 8 pts (28%) and poor in 6 pts (21%). 12 (41%) patients showed subcutaneous fibrosis at the last follow-up. LC, DFS and OS at five years was 92.3%, 86.3% and 91.2%, respectively. CONCLUSION: Although we analyzed a small number of patients, our results are satisfactory and this approach is feasible even if it could not be considered the standard treatment. Further clinical trials exploring IORT are needed to identify possible subgroups of patients that might be suitable for this type of approach.

Good clinical practice and the use of hypofractionation radiation schedules as weapons to reduce the risk of COVID-19 infections in radiation oncology unit: A mono-institutional experience.

BACKGROUND: After coronavirus disease outbreak emerged in 2019, radiotherapy departments had to adapt quickly their health system and establish new organizations and priorities. The purpose of this work is to report our experience in dealing with COVID-19 emergency, how we have reorganized our clinical activity, changed our priorities, and stressed the use of hypofractionation in the treatment of oncological diseases. MATERIALS AND METHODS: The patients' circuit of first medical examinations and follow-up was reorganized; a more extensive use of hypofractionated schedules was applied; a daily triage of the patients and staff, use of personal protective equipment, hand washing, environment sanitization, social distancing and limitations for the patients' caregivers in the department, unless absolutely essential, were performed; patients with suspected or confirmed COVID-19 were treated at the end of the day. In addition, the total number of radiotherapy treatment courses, patients and sessions, in the period from February 15 to April 30, 2020, comparing the same time period in 2018 were retrospectively investigated. In particular, changes in hypofractionated schedules adopted for the treatment of breast and prostate cancer and palliative bone metastasis were analyzed. RESULTS: Between February 15, and April 30, 2020, an increased number of treatments was carried out: Patients treated were overall 299 compared to 284 of the same period of 2018. Stressing the use of hypofractionation, 2036 RT sessions were performed, with a mean number of fractions per course of 6.8, compared to 3566 and 12.6, respectively, in 2018. For breast cancer, the schedule in 18 fractions has been abandoned and treatment course of 13 fractions has been introduced; a 27% reduction in the use of 40.5 Gy in 15 fractions, (67 treatments in 2018-49 in 2020) was reported. An increase of 13% of stereotactic body radiation therapy for prostate cancer was showed. The use of the 20 Gy in 4 or 5 sessions for the treatment of symptomatic bone metastasis decreased of 17.5% in favor of 8 Gy-single fraction. Three patients results COVID-19 positive swab: 1 during, 2 after treatment. Only one staff member developed an asymptomatic infection. CONCLUSIONS: The careful application of triage, anti-contagion and protective measures, a more extensive use of hypofractionation allowed us to maintain an effective and continuous RT service with no delayed/deferred treatment as evidenced by the very low number of patients developing COVID-19 infection during or in the short period after radiotherapy. Our experience has shown how the reorganization of the ward priority, the identification of risk factors with the relative containment measures can guarantee the care of oncological patients, who are potentially at greater risk of contracting the infection.

Stereotactic Body Radiation Therapy (SBRT) for Oligorecurrent/Oligoprogressive Mediastinal and Hilar Lymph Node Metastasis: A Systematic Review.

INTRODUCTION: Mediastinal or hilar lymph node metastases are a challenging condition in patients affected by solid tumors. Stereotactic body radiation therapy (SBRT) could play a crucial role in the therapeutic management and in the so-called "no-fly zone", delivering high doses of radiation in relatively few treatment fractions with excellent sparing of healthy surrounding tissues and low toxicity. The aim of this systematic review is to evaluate the feasibility and tolerability of SBRT in the treatment of mediastinal and hilar lesions with particular regard to the radiotherapy doses, dose constraints for organs at risk, and clinical outcomes. MATERIALS AND METHODS: Two blinded investigators performed a critical review of the Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), starting from a specific question: What is the clinical impact of SBRT for the treatment of oligorecurrent/oligoprogressive mediastinal and hilar metastasis? All retrospective and prospective clinical trials published in English up to February 2022 were analyzed. RESULTS: A total of 552 articles were identified and 12 of them were selected with a total number of 478 patients treated with SBRT for mediastinal or hilar node recurrence. All the studies are retrospective, published between 2015 and 2021 with a median follow-up ranging from 12 to 42.2 months. Studies following SBRT for lung lesions or retreatments after thorax radiotherapy for stage III lung cancer were also included. The studies showed extensive heterogeneity in terms of patient and treatment characteristics. Non-small cell lung cancer was the most frequently reported histology. Different dose schemes were used, with a higher prevalence of 4-8 Gy in 5 or 6 fractions, but dose escalation was also used up to 52 Gy in 4 fractions with dose constraints mainly derived from RTOG 0813 trial. The radiotherapy technique most frequently used was volumetric modulated arc therapy (VMAT) with a median PTV volume ranging from 7 to 25.7 cc. The clinical outcome seems to be very encouraging with 1-year local control (LC), overall survival (OS) and progression-free survival (PFS) rates ranging from 84 to 94%, 53 to 88% and 23 to 53.9%, respectively. Half of the studies did not report toxicity greater than G3 and only five cases of fatal toxicity were reported. CONCLUSIONS: From the present review, it is not possible to draw definitive conclusions because of the heterogeneity of the studies analyzed. However, SBRT appears to be a safe and effective option in the treatment of mediastinal and hilar lymph node recurrence, with a good toxicity profile. Its use in clinical practice is still limited, and there is extensive heterogeneity in patient selection and fractionation schedules. Good performance status, small PTV volume, absence of previous thoracic irradiation, and administration of a high biologically effective dose (BED) seem to be factors that correlate with greater local control and better survival rates. In the presence of symptoms related to the thoracic lymph nodes, SBRT determines a rapid control that lasts over time. We look forward to the prospective studies that are underway for definitive conclusions.

Adenoid Cystic Carcinoma/Basal Cell Carcinoma of the Prostate: Overview and Update on Rare Prostate Cancer Subtypes.

Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in the literature. Data on treatment options are scarce. The aim of our work was to retrospectively review the published reports. Thirty-three case reports or case series were analyzed (106 patients in total). Pathological features, management, and follow-up information were evaluated. Despite the relatively low level of evidence given the unavoidable lack of prospective trials for such a rare prostate tumor, the following considerations were made: prostate ACC/BCC is an aggressive tumor often presenting with locally advanced disease and incidental diagnosis occurs during transurethral resection of the prostate for urinary obstructive symptoms. Prostate-specific antigen was not a reliable marker for diagnosis nor follow-up. Adequate staging with Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) should be performed before treatment and during follow-up, while there is no evidence for the use of Positron Emission Tomography (PET). Radical surgery with negative margins and possibly adjuvant radiotherapy appear to be the treatments of choice. The response to androgen deprivation therapy was poor. Currently, there is no evidence of the use of truly effective systemic therapies.

The Role of Interstitial Brachytherapy for Breast Cancer Treatment: An Overview of Indications, Applications, and Technical Notes.

Breast cancer represents the second leading cause of cancer-related death in the female population, despite continuing advances in treatment options that have significantly accelerated in recent years. Conservative treatments have radically changed the concept of healing, also focusing on the psychological aspect of oncological treatments. In this scenario, radiotherapy plays a key role. Brachytherapy is an extremely versatile radiation technique that can be used in various settings for breast cancer treatment. Although it is invasive, technically complex, and requires a long learning curve, the dosimetric advantages and sparing of organs at risk are unequivocal. Literature data support muticatheter interstitial brachytherapy as the only method with strong scientific evidence to perform partial breast irradiation and reirradiation after previous conservative surgery and external beam radiotherapy, with longer follow-up than new, emerging radiation techniques, whose effectiveness is proven by over 20 years of experience. The aim of our work is to provide a comprehensive view of the use of interstitial brachytherapy to perform breast lumpectomy boost, breast-conserving accelerated partial breast irradiation, and salvage reirradiation for ipsilateral breast recurrence, with particular focus on the implant description, limits, and advantages of the technique.

Hypofractionated irradiation of infra-supraclavicular lymph nodes after axillary dissection in patients with breast cancer post-conservative surgery: impact on late toxicity.

BACKGROUND: The aim of the present work was to analyse the impact of mild hypofractionated radiotherapy (RT) of infra-supraclavicular lymph nodes after axillary dissection on late toxicity. METHODS: From 2007 to 2012, 100 females affected by breast cancer (pT1- T4, pN1-3, pMx) were treated with conservative surgery, Axillary Node Dissection (AND) and loco-regional radiotherapy (whole breast plus infra-supraclavicular fossa). Axillary lymph nodes metastases were confirmed in all women. The median age at diagnosis was 60 years (range 34-83). Tumors were classified according to molecular characteristics: luminal-A 59 pts (59%), luminal-B 24 pts (24%), basal-like 10 pts (10%), Her-2 like 7 pts (7%). 82 pts (82%) received hormonal therapy, 9 pts (9%) neo-adjuvant chemotherapy, 81pts (81%) adjuvant chemotherapy. All patients received a mild hypofractionated RT: 46 Gy in 20 fractions 4 times a week to whole breast and infra-supraclavicular fossa plus an additional weekly dose of 1,2 Gy to the lumpectomy area. The disease control and treatment related toxicity were analysed in follow-up visits. The extent of lymphedema was analysed by experts in Oncological Rehabilitation. RESULTS: Within a median follow-up of 50 months (range 19-82), 6 (6%) pts died, 1 pt (1%) had local progression disease, 2 pts (2%) developed distant metastasis and 1 subject (1%) presented both. In all patients the acute toxicity was mainly represented by erythema and patchy moist desquamation. At the end of radiotherapy 27 pts (27%) presented lymphedema, but only 10 cases (10%) seemed to be correlated to radiotherapy. None of the patients showed a severe damage to the brachial plexus, and the described cases of paresthesias could not definitely be attributed to RT. We did not observe symptomatic pneumonitis. CONCLUSIONS: Irradiation of infra-supraclavicular nodes with a mild hypofractionated schedule can be a safe and effective treatment without evidence of a significant increase of lymphedema appearance radiotherapy related.

Mono-institutional Italian experience with a double-lumen balloon-brachytherapy device for early breast cancer: results at a 5-year minimum follow-up.

AIMS AND BACKGROUND: To report the 5-year minimum follow-up in low-risk breast cancer patients treated with a double-lumen balloon-brachytherapy device in one mono-institutional Italian experience. Local control data and cosmetic outcomes were collected and analyzed. METHODS: Between October 2004 and December 2007, we treated 30 early stage breast cancer patients who underwent conservative surgery followed by adjuvant accelerated partial breast irradiation with a double-lumen balloon-brachytherapy system. Eligibility criteria for the protocol were based on the indications of the American Brachytherapy Society and the American Society of Breast Surgeons. The device was placed inside the lumpectomy cavity during surgery by open technique in all the patients. Computed tomography images and standard X-ray were used for treatment planning. The total irradiation dose was 34 Gy in 10 fractions of 3.4 Gy (twice daily) over 5 days to the lumpectomy cavity. RESULTS: Median follow-up was 80.5 months (range, 60-98). No patient developed local recurrence or distant metastasis. At the end of treatment, there was evidence of a symptomatic seroma in 83% of the total patients, with a yearly decreasing trend. However, the incidence of mild and moderate fibrosis progressively increased. Seventy-seven percent of the patients were satisfied with their cosmetic results. CONCLUSIONS: Our findings reinforce the hypothesis that an accelerated double-lumen balloon-breast brachytherapy catheter in selected low-risk patients is safe, and a favorable cosmetic outcome can be achieved.

Image guided hypofractionated radiotherapy by helical tomotherapy for prostate carcinoma: toxicity and impact on Nadir PSA.

AIM: To evaluate the toxicity of a hypofractionated schedule for primary radiotherapy (RT) of prostate cancer as well as the value of the nadir PSA (nPSA) and time to nadir PSA (tnPSA) as surrogate efficacy of treatment. MATERIAL AND METHODS: Eighty patients underwent hypofractionated schedule by Helical Tomotherapy (HT). A dose of 70.2 Gy was administered in 27 daily fractions of 2.6 Gy. Acute and late toxicities were graded on the RTOG/EORTC scales. The nPSA and the tnPSA for patients treated with exclusive RT were compared to an equal cohort of 20 patients treated with conventional fractionation and standard conformal radiotherapy. RESULTS: Most of patients (83%) did not develop acute gastrointestinal (GI) toxicity and 50% did not present genitourinary (GU) toxicity. After a median follow-up of 36 months only grade 1 of GU and GI was reported in 6 and 3 patients as late toxicity. Average tnPSA was 30 months. The median value of nPSA after exclusive RT with HT was 0.28 ng/mL and was significantly lower than the median nPSA (0.67 ng/mL) of the conventionally treated cohort (P = 0.02). CONCLUSIONS: Hypofractionated RT schedule with HT for prostate cancer treatment reports very low toxicity and reaches a low level of nPSA that might correlate with good outcomes.

Two different hypofractionated breast radiotherapy schedules for 113 patients with ductal carcinoma in situ: preliminary results.

AIM: To assess local control and cosmetic outcomes for two different hypofractionated radiotherapy schedules after breast-conserving surgery for ductal carcinoma in situ (DCIS). PATIENTS AND METHODS: A total of 113 breast-conserving operated patients with DCIS were treated from August 2006 to August 2011: 41 women received 46 Gy in 20 fractions of 2.3 Gy four times a week, for five weeks; the other 72 patients received 39 Gy in 13 fractions of 3 Gy four times a week for 3.5 weeks. Both schedules involved a concomitant boost to the tumor bed, with dose adjustment according to the surgical margins. RESULTS: The median follow-up is 30.5 months. Overall, the treatments were well-tolerated. The most common acute effect was erythema: grade 1 in 56.1% and 31.9% in the longer and in the shorter hypofractionated treatment, grade 2 in 9.8% and 0% of cases respectively. Late toxicity of fibrosis occurred at grade 1 in 19.6% and 15.3% respectively and at grade 2 in 0% and 2.8%. CONCLUSION: These results suggest that patients with DCIS can be safely treated with a shorter radiotherapy regimen.

Focus on the actual clinical target volume irradiated with intraoperative radiotherapy for breast cancer.

AIM: Intraoperative radiotherapy (IORT) has been investigated as an exclusive adjuvant treatment option for early-stage breast cancer (BC). We analysed our experience on the technical aspects of this innovative approach in terms of identification of breast volume actually to be treated during IORT. PATIENTS AND METHODS: A total of 315 patients at low risk of breast cancer recurrence underwent IORT as exclusive treatment after breast-conservative surgery. To evaluate the breast volume actually irradiated with IORT, we considered a sample of eight patients, chosen retrospectively as having enough clips to identify the tumour bed and IORT site in computed-tomography (CT). The clinical target volume (CTV) was assessed for each patient with two different methods: the first, cc-IORT, was considered during surgery according to the chosen collimator diameter and glandular thickness, while the second, cc-CT, was evaluated through computed-tomography performed after surgery. The cc-CT CTV was obtained by contouring the cc-IORT on the CT section on the basis of the clips placed by the surgeon on the resection margins. RESULTS: In our experience, the 5-cm (50%) and the 6-cm (36%) diameter collimators have been the ones, used the most. The diameter of the collimator used did not appear to adversely affect the satisfactory aesthetic result. The comparison between CTVs showed that glandular breast volume contoured with CT (cc-CT) appeared to be three fold larger than the target identified at surgery and included in the area of chosen collimator (cc-IORT). CONCLUSION: The actual volume of breast gland irradiated with the IORT procedure appears to be larger than expected. This may be due to the area being prepared for IORT by placing tissue compactly.