Image-guided moderately hypofractionated radiotherapy for localized prostate cancer: a multicentric retrospective study (IPOPROMISE).

BACKGROUND: Moderate hypofractionated radiotherapy is a treatment option for the cure of localized prostate cancer (PCa) patients based on the results of randomized prospective trials, but there is a clinical concern about the relatively short length of follow-up, and real-world results on outcome and toxicity based on cutting-edge techniques are lacking. The objective of this study is to present the long-term results of a large multicentric series. MATERIALS AND METHODS: We retrospectively evaluated 1325 PCa patients treated with daily volumetric image-guided hypofractionated radiotherapy between 2007 and 2020 in 16 Centers. For survival endpoints, we used Kaplan-Meier survival curves and fitted univariate and multivariable Cox's proportional hazards regression models to study the association between the clinical variables and each survival type. RESULTS: At the end of the follow-up, 11 patients died from PCa. The 15-year values of cancer-specific survival (CSS) and biochemical relapse-free survival (b-RFS) were 98.5% (95%CI 97.3-99.6%) and 85.5% (95%CI 81.9-89.4%), respectively. The multivariate analysis showed that baseline PSA, Gleason score, and the use of androgen deprivation therapy were significant variables for all the outcomes. Acute gastrointestinal (GI) and genitourinary (GU) toxicities of grade ≥ 2 were 7.0% and 16.98%, respectively. The 15-year late grade ≥ 2 GI and GU toxicities were 5% (95%CI 4-6%) and 6% (95%CI 4-8%), respectively. CONCLUSION: Real-world long-term results of this multicentric study on cutting-edge techniques for the cure of localized PCa demonstrated an excellent biochemical-free survival rate of 85.5% at 15 years, and very low rates of ≥ G3 late GU and GI toxicity (1.6% and 0.9% respectively), strengthening the results of the available published trials.

Immunogenicity after two and three doses of mRNA vaccine in patients with cancer treated with exclusive radiotherapy.

BACKGROUND AND PURPOSE: Data on immunoresponse after SARS-CoV-2 vaccines for patients treated with exclusive radiotherapy (RT) are scarce. Since RT may affect the immune system, we conducted the MORA trial (Antibody response and cell-mediated immunity of MOderna mRNA-1273 vaccine in patients treated with RAdiotherapy). MATERIALS AND METHODS: Data regarding humoral and cellular immune response of patients treated with RT were prospectively collected after the second and third dose of mRNA vaccines. RESULTS: Ninety-two patients were enrolled. With a median of 147 days after the second dose, the median SARS-CoV-2 IgG titer was 300 BAU/mL: six patients were seronegative (Spike IgG titer ≤ 40 BAU/mL), whereas 24, 46 and 16 were poor responders (Spike IgG titer:41-200 BAU/mL), responders (Spike IgG titer:201-800 BAU/mL) and ultraresponders (Spike IgG titer > 800 BAU/mL), respectively. Among seronegative patients, two patients were negative also for cell mediated response, as tested with IFN-γ release Assay (IGRA) test. With a median of 85 days after the third dose, the median SARS-CoV-2 IgG titer was 1632 BAU/mL in 81 patients: only two patients were seronegative, whereas 16 and 63 patients were responders and ultraresponders, respectively. Among the 2 persistently seronegative patients, IGRA test was negative in one who had previously received anti-CD20 therapy. Documented paucisymptomatic (n = 3) or asymptomatic (n = 4) infection occurred after the third dose, during the Omicron wave. CONCLUSION: In patients treated with exclusive RT, even during the Omicron breakthrough, robust humoral response and clinical protection from severe SARS-CoV-2 disease were achievable with three doses of mRNA vaccine.

The role of EPID in vivo dosimetry in the risk management of stereotactic lung treatments.

BACKGROUND AND OBJECTIVE: In this work we report our experience with the use of in vivo dosimetry (IVD) in the risk management of stereotactic lung treatments. METHODS: A commercial software based on the electronic portal imaging device (EPID) signal was used to reconstruct the actual planning target volume (PTV) dose of stereotactic lung treatments. The study was designed in two phases: i) in the observational phase, the IVD results of 41 consecutive patients were reviewed and out-of-tolerance cases were studied for root cause analysis; ii) in the active phase, the IVD results of 52 patients were analyzed and corrective actions were taken when needed. Moreover, proactive preventions were further introduced to reduce the risk of future failures. The error occurrence rate was analyzed to evaluate the effectiveness of proactive actions. RESULTS: A total of 330 fractions were analyzed. In the first phase, 13 errors were identified. In the active phase, 12 errors were detected, 5 of which needed corrective actions; in 4 patients the actions taken corrected the error. Several preventions and barriers were introduced to reduce the risk of future failures: the planning checklist was updated, the procedure for vacuum pillows was improved, and use of the respiratory compression belt was optimized. A decrease in the failure rate was observed, showing the effectiveness of procedural adjustment. CONCLUSION: The use of IVD allowed the quality of lung stereotactic body radiation therapy (SBRT) treatments to be improved. Patient-specific and procedural corrective actions were successfully taken as part of risk management, leading to an overall improvement in the dosimetric accuracy.

Choline PET/CT in recurrent prostate cancer.

Purpose: Biochemical recurrence (BR) occurs in up to 40% of patients with prostate cancer (PCa) treated with primary radical prostatectomy (RP). Choline PET/CT may show, in a single-step examination, the site of tumor recurrence earlier than traditional imaging methods, particularly at low prostate-specific antigen (PSA) levels, thus influencing subsequent treatment. Methods/patients: Patients with recurrent and non-metastatic prostate cancer (nmPCa), who were assessed with choline PET/CT, were included in the analysis. Based on imaging results, the following therapeutic strategies were chosen: radiotherapy to the prostatic bed, androgen deprivation therapy (ADT), and chemotherapy or stereotactic body radiotherapy (SBRT) to either the pelvic lymph nodes or distant metastases. We assessed the impact of age, PSA levels, Gleason score (GS), and adjuvant therapy on oncological outcomes. Results: Data from 410 consecutive nmPCa patients with BR who underwent RP as primary treatment were analyzed. One hundred seventy-six (42.9%) patients had a negative choline PET/CT, and 234 (57.1%) patients resulted positive. In the multivariate analysis, only chemotherapy and PSA at recurrence were significant independent prognostic factors on overall survival (OS). In the PET-positive subgroup, the number of relapses, PSA post-prostatectomy, and chemotherapy impacted on OS. PSA (post-surgery and at recurrence) affected progression-free survival (PFS) in the univariate analysis. In the multivariate analysis, GS, the number of relapse sites, and PSA (post-surgery and at recurrence) were significant prognostic factors for disease-free survival (DFS). Conclusion: Choline PET/CT provides better accuracy than conventional imaging for the assessment of nmPCa with BR after prostatectomy, thereby enabling salvage strategies and improving quality of life.

Clinical implementation of 3D in vivo dosimetry for abdominal and pelvic stereotactic treatments.

PURPOSE: To analyze results from three years of in vivo transit EPID dosimetry of abdominal and pelvic stereotactic radiotherapy and to establish tolerance levels for routine clinical use. MATERIAL: 80 stereotactic VMAT treatments (152 fractions) targeting the abdomen or pelvis were analyzed. In vivo 3D doses were reconstructed with an EPID commercial algorithm. Gamma Agreement Index (GAI) and DVH differences in Planning Target Volume (PTV) and Clinical Target Volume (CTV) were evaluated. Initial tolerance level was set to GAI > 85% in PTV. Fractions Over Tolerance Level (OTL) were deemed to be due to set-up errors, incorrect use of immobilization devices, 4D errors, transit EPID algorithm errors and unknown/unidentified errors. Statistical Process Control (SPC) was applied to determine local tolerance levels. RESULTS: Average GAI were (82.7 ± 20.9) % in PTV and (72.9 ± 29.7) % in CTV. 37.8% of fractions resulted OTL and were classified as: set-up errors (3.3%), incorrect use of immobilization devices (2.1%), 4D errors (2.1%), EPID transit algorithm errors (17.1%). OTL causes for the remaining 13.2% of fractions were not identified. The differences between PTV and CTV measured in vivo and calculated mean dose (average difference ± standard deviation) were (-3.3% ± 3.2%) and (-2.3% ± 3.0%). When tolerance levels based on SPC to PTV mean dose differences were applied, the percentage of OTL decreased to 7% and no EPID algorithm error occurred. One error was not identified. CONCLUSIONS: The application of local tolerance levels to EPID in vivo dosimetry proved to be useful for detecting extra-lung SBRT treatment errors.

Combining Abiraterone and Radiotherapy in Prostate Cancer Patients Who Progressed During Abiraterone Therapy.

BACKGROUND/AIM: This multicenter, retrospective, 'field-practice' study investigated treatment outcomes of ongoing abiraterone therapy with the addition of radiotherapy (RT) - initiated for oligoprogression or with a palliative intent. PATIENTS AND METHODS: Consecutive patients affected by metastatic castration-resistant prostate cancer (mCRPC) treated with abiraterone acetate were considered if they had received RT after the initiation of abiraterone treatment. RESULTS: A total of 32 patients were enrolled in the study. Median duration of abiraterone treatment was 13.0 months (range=3.8-40.9 months). Median duration of abiraterone treatment before RT was 5.9 months (range=0.4-40.0 months), and 7.2 months after RT (range=0.1-29.7 months). Median progression-free survival (PFS) was 12.6 months (95%CI=10.5-14.7) from the initiation of abiraterone treatment. From RT administration, PFS was 9.6 months (95%CI=6.4-12.9). Median overall survival (OS) since abiraterone initiation was 18.9 months (95%CI=4.7-33.0). CONCLUSION: RT prolongs abiraterone treatment in mCRPC patients leading to better clinical outcomes with this molecule.

Loco regional failure pattern after lumpectomy and breast irradiation in 4,185 patients with T1 and T2 breast cancer. Implications for nodal irradiation.

The aim of this study is to determinate incidence and risk factors for loco regional failure (LRR) (breast, supraclavicular, axillary and internal mammary nodes) and indications for nodal irradiation. From January 1980 to December 2001, 4,185 patients with T1-T2 breast cancer were treated with conservative surgery and whole breast radiotherapy without nodal irradiation at the University of Florence. The median age was 55 years (range 19-86). All patients were followed for a median of eight years (range 3 months to 20 years). Multivariate analysis showed as independent prognostic factors for isolated nodal relapse (NR) the presence of more than three positive lymph nodes (PAN) (p = 0.001), angiolymphatic invasion (p = 0.002) and pT2 (p = 0.02). However, only 4.8% of patients with more than three PAN developed NR as the only site of recurrence. Having one to three PAN was not associated with an increased risk of NR. We believe that it is not necessary to prescribe nodal irradiation to patients with negative or one to three PAN. Regarding patients with more than three PAN, the number of isolated NR is also small to routinely justify a node irradiation.

Breast cancer in the elderly: treatment of 1500 patients.

There is a significant difference in the extent of treatment offered to the elderly with breast cancer; in the United States, while 98% of patients less than 65 years of age receive standard treatment, 81% of those older than 65 years were treated according to protocol. This study's goal was to evaluate disease-specific survival and local-regional recurrence in breast cancer patients more than 65 years of age at diagnosis. A total of 1500 patients with invasive breast carcinoma were treated consecutively from May 1971 to July 2002 at the University of Florence, Florence, Italy. All patients were more than 65 years of age. The median age was 70.6 years (range 65.1-87.3 years). The median follow-up was 8.7 years (range 1-30 years). The crude probability of survival (or relapse occurrence) was estimated using the Kaplan-Meier method and survival (or relapse occurrence) comparisons were carried out using Cox proportional hazard regression models. The Cox regression model by stepwise selection showed as independent prognostic factors for disease-specific survival (DSS), the occurrence of a local relapse (p < 0.0001), pN status (p < 0.0001), the type of surgery (p < 0.0001), and the use of radiotherapy (p < 0.0006) and chemotherapy (p = 0.01). For local disease-free survival (LDFS), the Cox regression model by stepwise selection showed that mastectomy (p < 0.0001), histotype (p < 0.0001), pN status (p < 0.0001), and pT status (p = 0.001) were the only independent prognostic factors. Age was not a prognostic factor for DSS nor LDFS. We suggest treating patients with appropriate treatment for their prognostic factors.

Late treatment-related complications in 214 patients with extremity soft-tissue sarcoma treated by surgery and postoperative radiation therapy.

BACKGROUND: We assessed the occurrence of long-bone fracture and other side effects in a group of 214 consecutive patients who underwent radical excision for soft-tissue sarcoma of the limb followed by postoperative irradiation. METHODS: Two hundred fourteen patients underwent postoperative irradiation after radical excision of soft-tissue sarcoma of the limb; 156 (73%) received postoperative brachytherapy (BRT) plus external-beam radiation therapy (EBRT), and 58 (27%) underwent postoperative EBRT only. All patients were followed-up for a median time of 4.5 years (range 3 months to 10 years). RESULTS: Seven patients developed bone fracture, which is considered severe morbidity; time between surgery and occurrence of fracture ranged between 10 and 72 months (average 31). Severe sclerosis with impairment of limb function was diagnosed in 5 and peripheral nerve damage in 3 patients. Wound complications were detected in 8 patients. CONCLUSIONS: In our series, no statistically significant correlation between bone fracture and clinical features or "technical" parameters was found, but all of the patients who experienced bone fracture (7 of 7) were postmenopausal women >55 years old.

Accelerated intensity-modulated external radiotherapy as a new technical approach to treat the index quadrant after conserving surgery in early breast cancer: a preliminary study.

PURPOSE: We present a novel technical approach to treat the index quadrant after conserving surgery in patients with early breast cancer and study its clinical feasibility. METHODS AND MATERIAL: Patients selected for the study, after breast conserving surgery with histologically verified breast carcinoma, signed a full informed consent to intensity-modulated external radiotherapy of the partial breast. Treatment was performed with the 6 MV beam from one of the Elekta Precise LINAC units installed in our Department. The prescribed dose was 30 Gy in 5 fractions in 10 days. RESULTS: Acute toxicity was minimal. No skin changes were noted during treatment or during the first 6 months after radiotherapy treatment. CONCLUSIONS: Accelerated partial breast irradiation using intensity-modulated external radiotherapy is technically feasible. We think the approach will give good results in terms of local control, toxicity and quality of life, at the same time sparing resources for the patient and health care system.

Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. I. The case of T1N0 disease.

PURPOSE: To retrospectively evaluate local control rates, late damage incidence, functional results, and second tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T1 glottic cancer. METHODS AND MATERIALS: A total of 831 T1 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia-Istituto del Radio "O. Alberti" (BS) were studied. Actuarial cumulative local control probability (LC), disease-specific (DSS), and overall survival (OS) rates have been calculated and compared in the different clinical and therapeutic subgroups with both univariate and multivariate analysis. Types of relapse and their surgical salvage have been evaluated, along with the functional results of treatment. Late damage incidence and second tumor cumulative probability (STP) have been also calculated. RESULTS: In the entire series, 3-, 5-, and 10-year OS was equal to 86%, 77%, and 57%, respectively. Corresponding values for LC were 86%, 84%, and 83% and for DSS 96%, 95%, and 93%, taking into account surgical salvage of relapsed cases. Eighty-seven percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were: male gender, earlier treatment period, larger tumor extent, anterior commissure involvement, and the use of Cobalt 60. At multivariate analysis, only gender, tumor extent, anterior commissure involvement, and beam type retained statistical significance. Higher total doses and larger field sizes are significantly related (logistic regression) with a higher late damage incidence. Scatterplot analysis of various combinations of field dimensions and total dose showed that field dimensions >35 and <49 cm2, together with doses of >65 Gy, offer the best local control results together with an acceptably low late damage incidence. Twenty-year STP was equal to 23%, with second tumor deaths being more frequent than larynx cancer deaths (67 of 831 vs. 46/831). CONCLUSION: The results of this study support the opinion, suggested by some international guidelines, that radiotherapy is standard treatment for T1 glottic cancer. Better results are obtained in patients with less extended disease and with 4-6 MV photon beams. The use of doses in excess of 65 Gy and of field sizes of 36-49 cm2 is probably the best technical choice available. Late damage is infrequent, but careful follow-up is warranted to detect early not only relapses (because conservative salvage surgery is feasible), but also second malignant tumors, which constitute the main cause of death in these patients and are potentially curable.

Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. II. The case of T2N0 disease.

PURPOSE: To retrospectively evaluate local control rates, late damage incidence, functional results, and second-tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T2 glottic cancer. METHODS AND MATERIALS: A total of 256 T2 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia, Istituto del Radio "O. Alberti" (BS) were studied. Cumulative probability of local control (LC), disease-specific survival (DSS), and overall survival (OS) rates were calculated and compared in the different clinical and therapeutic subgroups by both univariate and multivariate analysis. Types of relapse and their surgical salvage were evaluated, along with the functional results of treatment. Late-damage incidence and second-tumor cumulative probability (STP) were also calculated. RESULTS: In the entire series, 3-year, 5-year, and 10-year OS rates were, respectively, 73%, 59%, and 37%. Corresponding values for cumulative LC probability were 73%, 73%, and 70% and for DSS, 89%, 86%, and 85%, taking into account surgical salvage of relapsed cases. Seventy-three percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were larger tumor extent and impaired cord mobility. At multivariate analysis, the same factors retained statistical significance. Twenty-year STP was 23%, with second-tumor deaths less frequent than larynx cancer deaths (20 of 256 vs. 30 of 256). Incidence of late damage was higher in the first decade of accrual (22%) than in the last decade (10%, p = 0.03); the same was true for severe late damage (9% vs. 1.8%). CONCLUSION: Present-day radical radiotherapy can be considered a standard treatment for T2 glottic cancer. Better results are obtained in patients with less extended disease. Late damage is relatively infrequent, but a careful follow-up is warranted for early detection not only of relapses (because salvage surgery is feasible) but also of second malignant tumors, which constitute a relevant but not the leading cause of death in these patients and are potentially curable.