Use of Thermoluminescence Dosimetry for QA in High-Dose-Rate Skin Surface Brachytherapy with Custom-Flap Applicator.

Surface brachytherapy (BT) lacks standard quality assurance (QA) protocols. Commercially available treatment planning systems (TPSs) are based on a dose calculation formalism that assumes the patient is made of water, resulting in potential deviations between planned and delivered doses. Here, a method for treatment plan verification for skin surface BT is reported. Chips of thermoluminescent dosimeters (TLDs) were used for dose point measurements. High-dose-rate treatments were simulated and delivered through a custom-flap applicator provided with four fixed catheters to guide the Iridium-192 (Ir-192) source by way of a remote afterloading system. A flat water-equivalent phantom was used to simulate patient skin. Elekta TPS Oncentra Brachy was used for planning. TLDs were calibrated to Ir-192 through an indirect method of linear interpolation between calibration factors (CFs) measured for 250 kV X-rays, Cesium-137, and Cobalt-60. Subsequently, plans were designed and delivered to test the reproducibility of the irradiation set-up and to make comparisons between planned and delivered dose. The obtained CF for Ir-192 was (4.96 ± 0.25) µC/Gy. Deviations between measured and TPS calculated doses for multi-catheter treatment configuration ranged from -8.4% to 13.3% with an average of 0.6%. TLDs could be included in clinical practice for QA in skin BT with a customized flap applicator.

Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer.

Immunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune resistance and escape need to be better investigated. Here, we review the major mechanisms of immune escape activated by the indolamine 2,3-dioxygenase 1 (IDO1) pathway in EC and focus on potential therapeutic strategies based on IDO1 signaling pathway control. IDO1 catalyzes the first rate-limiting step of the so-called "kynurenine (Kyn) pathway", which converts the essential amino acid l-tryptophan into the immunosuppressive metabolite l-kynurenine. Functionally, IDO1 has played a pivotal role in cancer immune escape by catalyzing the initial step of the Kyn pathway. The overexpression of IDO1 is also associated with poor prognosis in EC. These findings can lead to advantages in immunotherapy-based approaches as a rationale for overcoming the immune escape. Indeed, besides immune checkpoints, other mechanisms, including the IDO enzymes, contribute to the EC progression due to the immunosuppression induced by the tumor milieu. On the other hand, the IDO1 enzyme has recently emerged as both a promising therapeutic target and an unfavorable prognostic biomarker. This evidence provides the basis for translational strategies of immune combination, whereas IDO1 expression would serve as a potential prognostic biomarker in metastatic EC.

Management of Metastatic Disease in Campania (MAMETIC): An Observational Multicenter Retrospective and Prospective Trial on Palliative Radiotherapy in an Italian Region. Study Protocol.

Background: In the Italian Campania Region, 30.517 new cases of solid cancer have been diagnosed, in 2019. Of those, patients with metastatic disease are up to 20%. This class of patients is extremely diversified and copious, and the offer of radiotherapy may vary in different geographical areas within the same region. The aim of this observational multicenter retrospective and prospective trial is to evaluate the occurrence of metastatic metastatic cancer patients candidates for palliative radiotherapy in several areas of a great Italian region, the management of the disease through RT approaches, and its impact on cancer-related pain and overall HRQoL. Methods: This is a multicenter, retrospective and prospective observational investigation. The retrospective part of the study concerns all patients enrolled with a diagnosis of metastatic disease and treated in RT centers within the Campania Region between January 2019 and July 2020. The prospective phase is going to involve all the metastatic patients with an indication of palliative RT. Considering regional epidemiological data, we expect an enrollment of 12.500-21.000 patients in 5 years. Conclusion: The MAMETIC Trial in an observational study designed for investigating on the use of radiotherapy in patients with advanced disease within a regional area, and for evaluating the local response to the patient's request. It can be a unique opportunity, not only to highlight possible geographic differences but also to regularly collect and share data to standardize the therapeutic offer within the regional area. ClinicalTrials.gov ID NCT04595032, retrospectively registered.

Can the Day 0 CT-scan predict the post-implant scanning? Results from 136 prostate cancer patients.

PURPOSE: Post-implant CT-scanning is an essential part of permanent prostate brachytherapy. However, the evaluation of post-implant CT dosimetry is not straightforward due to the edema that can modify the dose to the prostate and to the organs at risk. The aim of this study is to evaluate the impact of the timing of the post-implant CT-scan on the dosimetric results and to verify if the Day 0 scan findings can predict Day 50 scanning. METHODS: 136 consecutive patients who received monotherapy with I-125 implants were selected for this study. Two sets of 8 dosimetric quality parameters corresponding to 2 different CT-scans (Day 0 and Day 50) were calculated and compared. The dosimetric parameters included are the percentage volume of the post-implant prostate receiving 80%, 100% and 150% of the prescribed dose, the doses covering 80% and 90% of the prostate volume and the Dose Homogeneity Index. The values of the dose covering 1cm3 of the rectum and urethra were assessed. RESULTS: All the dosimetric parameters of the Day 50 were higher than those of the Day 0 scan. Linear functions were obtained that calculate D90 and V100 values at Day 50 based on the Day 0 findings. Rectal and urethral parameters tended to be underestimated on Day 0 CT-scan relative to Day 50 based dosimetry. CONCLUSIONS: Predicting the Day 50 dosimetry from the Day 0 scan could be a possible alternative to a Day 50 scan only in specific situations, but with a degree of uncertainty in the predicted values.

Postoperative management of keloids: low-dose-rate and high-dose-rate brachytherapy.

PURPOSE: We report the experience of the Radiation Oncology Department of the European Institute of Oncology in Milan, Italy, on the adjuvant low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy. Brachytherapy might be useful to improve keloids recurrence rate or reduce keloids treatment side effects instead of external beam radiotherapy. METHODS AND MATERIALS: Data on 70 consecutive patients treated after complete keloid surgical excision were retrospectively analyzed. First 38 patients and 46 keloids were treated with adjuvant LDR brachytherapy and the following 39 patients and 50 keloids underwent HDR treatment. Median delivered dose of LDR therapy was 16 Gy; HDR median dose was 12 Gy. Sixty-four keloids (66.7%) were symptomatic at diagnosis with pain, itching, or stress. RESULTS: Fourteen relapses over 46 treated keloids (30.4%) were observed in the LDR group and 19 of 50 keloids (38%) in the HDR group (p = 0.521). Recurrence rate was significantly higher in males (p = 0.009), in patients younger than 44 years (p < 0.0001), for arms, neck, and chest wall anatomic sites (p = 0.0001) and for symptomatic keloids (p = 0.017). Aesthetic outcome was better in case of larger keloids (>8 cm) (p = 0.064). Symptomatic relief was achieved in 92% of HDR patients and only 68% of LDR patients (p = 0.032). CONCLUSIONS: Postoperative brachytherapy is an effective treatment for keloids. In our study, LDR and HDR treatments resulted in similar recurrence rate. Better symptomatic relief was reported in case of HDR treatment compared with the LDR regimen.

Linac-based stereotactic body radiotherapy for oligometastatic patients with single abdominal lymph node recurrent cancer.

OBJECTIVES: To evaluate stereotactic body radiotherapy (SBRT) for single abdominal lymph node cancer recurrence. METHODS: Inclusion criteria for this retrospective study were as follows: adult oligometastatic cancer patients with single abdominal lymph node recurrence that underwent SBRT but not other local therapy, written informed consent for treatment. Previous radiotherapy or concomitant systemic therapy were allowed. Toxicity and tumor response were evaluated using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Scale and Response Evaluation Criteria in Solid Tumors. RESULTS: Sixty-nine patients (94 lesions) underwent SBRT (median 24 Gy/3 fractions). Primary diagnosis included urological, gastrointestinal, gynecologic, and other malignancies. Concomitant systemic therapy was performed in 35 cases. Median follow-up was 20 months. Two grade 3 acute and 1 grade 4 late toxicity events were registered. Complete radiologic response, partial response, stabilization, and progressive disease were observed in 36 (44%), 21 (26%), 20 (25%), and 4 (5%) lesions, respectively, out of 81 evaluable lesions. Response rates were similar when analysis was restricted to lesions treated with exclusive SBRT (no concomitant therapy). Actuarial 3-year in-field progression-free interval, progression-free survival and overall-survival rates were 64.3%, 11.7%, and 49.9%, respectively. Overall-survival rates were significantly higher in favorable histology cases (prostate and kidney tumors). Pattern of failure was predominantly out-field. CONCLUSIONS: SBRT is a feasible approach for single abdominal lymph node recurrence, offering excellent in-field tumor control with low-toxicity profile. Future studies are warranted to identify the patients that benefit most from this treatment. The optimal combination with systemic treatment should also be defined.

Image guided hypofractionated radiotherapy and quality of life for localized prostate cancer: prospective longitudinal study in 337 patients.

PURPOSE: We prospectively analyzed quality of life in a cohort of patients with prostate cancer undergoing a course of hypofractionated image guided radiotherapy. MATERIALS AND METHODS: Between August 2006 and January 2011, 337 patients with a median age of 73 years who had cT1-T2N0M0 prostate cancer were eligible for this prospective, longitudinal study of hypofractionated image guided radiotherapy (70.2 Gy/26 fractions) using 1 of 3 image guided radiotherapy modalities (transabdominal ultrasound, x-ray or cone beam computerized tomography) available in our radiation oncology department. Patients completed 4 questionnaires before treatment, and 6, 12 and 24 months later, including the International Index of Erectile Function-5, International Prostate Symptom Score, and EORTC (European Organization for Research and Treatment of Cancer) prostate cancer specific QLQ-PR25 and QLQ-C30. RESULTS: Patient followup was updated to at least the last questionnaire time point. Median followup was 19 months. Significant deterioration in erectile function on the International Index of Erectile Function-5 was documented with time only in patients without androgen deprivation (p = 0.0002). No change with time was observed in urinary symptom related quality of life on the QLQ-PR25 or International Prostate Symptom Score. Slight deterioration in QLQ-PR25 bowel symptom related quality of life was observed (p = 0.02). Overall QLQ-C30 Global Health Status improved with time (p = 0.03). On univariate analysis it significantly correlated with the maximum RTOG (Radiation Therapy Oncology Group)/EORTC urinary and bowel late toxicity scores after radiotherapy. CONCLUSIONS: The regimen of hypofractionated image guided radiotherapy with multiple imaging modalities adopted in our radiation oncology department for localized prostate cancer might be a successful strategy for dose escalation with a limited impact on different aspects of quality of life with time.

High-dose-rate interstitial brachytherapy in early stage buccal mucosa and lip cancer: report on 12 consecutive patients and review of the literature.

AIMS AND BACKGROUND: To evaluate clinical outcome and toxicity using high-dose-rate brachytherapy as monotherapy in head and neck carcinomas. METHODS: Between September 2004 and April 2010, a series of 12 patients with lip (7 patients) or buccal mucosa (5 patients) cancers were treated by exclusive interstitial high-dose-rate brachytherapy. The median age of the patients was 71.5 years (range, 47-87). Stages were T1N0M0 and T2N0M0 in 6 and 6 patients, respectively. A dose of 27 to 54 Gy in 9 to 16 fractions, 3 to 4.5 Gy per fraction, 2 fractions per day with a minimal gap of 6 h in between was delivered. RESULTS: After a median follow-up of 46 months (range, 10-85), the disease-free and overall survival was 83% (10 of 12 patients) and 50% (6 of 12 patients), respectively. The crude local control in the lip cancer patients was 100% and in the buccal mucosa cancer patients was 60%. No severe toxicity was registered. CONCLUSIONS: High-dose-rate brachytherapy is feasible and safe and offers the possibility to treat patients in an outpatient regimen.

Robotic image-guided stereotactic radiotherapy, for isolated recurrent primary, lymph node or metastatic prostate cancer.

PURPOSE: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. METHODS AND MATERIALS: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [(11)C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). RESULTS: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. CONCLUSIONS: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor control and a low toxicity profile. Further investigation is warranted to identify the patients who benefit most from this treatment modality. The optimal combination with androgen deprivation should also be defined.

Acute toxicity of image-guided hypofractionated radiotherapy for prostate cancer: nonrandomized comparison with conventional fractionation.

OBJECTIVES: To compare acute toxicity of prostate cancer image-guided hypofractionated radiotherapy (hypo-IGRT) with conventional fractionation without image-guidance (non-IGRT). To test the hypothesis that the potentially injurious effect of hypofractionation can be counterbalanced by the reduced irradiated normal tissue volume using IGRT approach. MATERIALS AND METHODS: One hundred seventy-nine cT1-T2N0M0 prostate cancer patients were treated within the prospective study with 70.2 Gy/26 fractions (equivalent to 84 Gy/42 fractions, α/ß 1.5 Gy) using IGRT (transabdominal ultrasound, ExacTrac X-Ray system, or cone-beam computer tomography). Their prospectively collected data were compared with data of 174 patients treated to 80 Gy/40 fractions with non-IGRT. The difference between hypo-IGRT and non-IGRT cohorts included fractionation (hypofractionation vs. conventional fractionation), margins (hypo-IGRT margins: 7 mm and 3 mm, for all but posterior margins; respectively; non-IGRT margins: 10 and 5 mm, for all but posterior margins, respectively), and use of image-guidance or not. Multivariate analysis was performed to define the tumor-, patient-, and treatment-related predictors for acute toxicity. RESULTS: All patients completed the prescribed radiotherapy course. Acute toxicity in the hypo-IGRT cohort included rectal (G1: 29.1%; G2: 11.2%; G3: 1.1%) and urinary events (G1: 33.5%; G2: 39.1%; G3: 5%). Acute toxicity in the non-IGRT patients included rectal (G1: 16.1%; G2: 6.3%) and urinary events (G1: 36.2%; G2: 20.7%; G3: 0.6%). In 1 hypo-IGRT and 2 non-IGRT patients, radiotherapy was temporarily interrupted due to acute toxicity. The incidence of mild (G1-2) rectal and bladder complications was significantly higher for hypo-IGRT (P = 0.0014 and P < 0.0001, respectively). Multivariate analysis showed that hypo-IGRT (P = 0.001) and higher PSA (P = 0.046) are correlated with higher acute urinary toxicity. No independent factor was identified for acute rectal toxicity. No significant impact of IGRT system on acute toxicity was observed. CONCLUSIONS: The acute toxicity rates were low and similar in both study groups with some increase in mild acute urinary injury in the hypo-IGRT patients (most probably due to the under-reporting in the retrospectively analyzed non-IGRT cohort). The higher incidence of acute bowel reactions observed in hypo-IGRT group was not significant in the multivariate analysis. Further investigation is warranted in order to exclude the bias due to the nonrandomized character of the study.

Correlation between acute and late toxicity in 973 prostate cancer patients treated with three-dimensional conformal external beam radiotherapy.

PURPOSE: To analyze the correlation between acute and late injury in 973 prostate cancer patients treated with radiotherapy and to evaluate the effect of patient-, tumor-, and treatment-related variables on toxicity. METHODS AND MATERIALS: Of the 973 patients, 542 and 431 received definitive or postprostatectomy radiotherapy, respectively. Three-dimensional conformal radiotherapy included a six-field technique and two-dynamic arc therapy. Toxicity was classified according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. The correlation between acute and late toxicity (incidence and severity) was assessed. RESULTS: Multivariate analysis showed that age 70 Gy (p = .014), and radiotherapy duration (p = .05) correlated with greater acute urinary toxicity. Acute rectal toxicity (p <.0001) was the only factor that correlated with late rectal injury on multivariate analysis. Late urinary toxicity correlated with acute urinary events (p <.0001) and was inversely related to the use of salvage radiotherapy (p = .018). A highly significant correlation was found between the incidence of acute and late events for both rectal (p <.001) and urinary (p <.001) reactions. The severity of acute toxicity (Grade 2 or greater) was predictive for the severity of late toxicity for both rectal and urinary events (p <.001). CONCLUSION: The results of our study have shown that the risk of acute reactions depends on both patient-related (age) and treatment-related (dose, technique) factors. Acute toxicity was an independent significant predictor of late toxicity. These findings might help to predict and prevent late radiotherapy-induced complications.