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.

Does cytoreductive surgery followed by adjuvant chemo-radiotherapy decrease the risk of recurrence and death in stage III endometrial cancer?

INTRODUCTION: The optimal postoperative adjuvant treatment for stage III endometrial cancer (EC) is controversial. The aim of the study was to evaluate the impact of cytoreductive surgery (CRS) and adjuvant chemoradiotherapy (CRT) on relapse-free survival (RFS) and overall survival (OS) in stage III EC. METHODS: Data on 36 patients with stage III EC were reviewed. A review of the literature was performed. RESULTS: Median follow-up was 31 months (range 3-195). All patients underwent radical surgery with lymph nodes assessment in 29 (80.6%). The histologic specimen revealed 27 (75%) type I and 9 (25%) type II cancers staged IIIA, IIIB, IIIC1, and IIIC2 in 9 (25%), 3 (8.3%), 17 (47.2%), and 7 (19.5%) patients, respectively. At the end of surgery, 32 (88.9%) had no residual tumor. Eighteen (50%) patients were treated with CRT (50% with sandwich approach, 50% with concurrent chemotherapy [CT]), 4 (11.1%) patients received radiotherapy (RT), and 14 (38.9%) had multiagent CT. Four patients (11.1%) with a residual tumor larger than 1 centimeter after surgery died of disease. The 5-year median recurrent free survival (RFS) for CRT, RT, and CT was 69.1%, 37.5%, and 23.8%, respectively (p = 0.05); the 5-year OS for CRT, RT, and CT was 83%, 35.7%, and 25%, respectively (p = 0.023). Multivariate analyses showed residual tumor as independent predictor for recurrence and death. CRT showed a borderline significance on OS. CONCLUSIONS: Our study demonstrated that optimal cytoreduction is the most significant prognostic factor and adjuvant CRT seems to be associated with a significant decreased risk of recurrence in stage III EC.

Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

Postoperative radiotherapy with volumetric modulated arc therapy of lacrimal gland carcinoma: two case reports and literature review.

AIMS: To evaluate technical issues and clinical outcomes after postoperative volumetric-modulated arc therapy (VMAT) in two cases of malignant lacrimal gland cancer. PATIENTS & METHODS: Patients were treated by postoperative VMAT and post-treatment clinical outcomes were followed-up to 18 months. RESULTS: Dosimetric results were acceptable and acute toxicity was manageable in both patients. No evidence of disease was found at latest follow-up. One patient underwent corneal transplant for central corneal ulceration, experiencing reduction of visual acuity. CONCLUSION: Postoperative VMAT for treatment of lacrimal gland tumors offers improved outcome, with manageable side effects. In the context of photon beam radiotherapy, VMAT emerged as a valuable treatment option for these malignant tumors.

Radiotherapy for unresectable sinonasal cancers: dosimetric comparison of intensity modulated radiation therapy with coplanar and non-coplanar volumetric modulated arc therapy.

BACKGROUND AND PURPOSE: To compare volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) plans for treatment of unresectable paranasal sinuses cancers (PNSCs) with different clinical presentations. MATERIAL AND METHODS: Four patients treated for primary target volume only (group 1), four requiring elective nodal irradiation (group 2) and four with positive nodes in macroscopic disease (group 3) were selected. For each patient were generated 7 fields IMRT, coplanar VMAT (c-VMAT) and non-coplanar VMAT (nc-VMAT) treatment plans. Total doses were 70Gy and 54Gy to high dose planning target volume (HD-PTV) and low-dose-PTV, respectively. Dose-volume histogram, conformity and homogeneity index (CI and HI), and monitor units (MUs) per Gy were evaluated. RESULTS: VMAT provided significantly better target coverage, in terms of V100% (Volume encompassed by the isodose 100%), than IMRT, in particular when nc-VMAT was used. In general, organ at risk sparing is similar with the three approaches, although nc-VMAT can allow a statistically significant reduction of dose to contralateral parotid gland and cochlea for all three groups. CONCLUSIONS: VMAT can offer significant improvement of treatment for all unresectable PNSCs over existing IMRT techniques. In particular, nc-VMAT may be a further advantage for those patients with sinonasal cancers and involvement of the nodes in whom large volumes and complex/irregular shape have to be irradiated, even if clinical benefits should be established in the future.

Contouring of the Pharyngeal Superior Constrictor Muscle (PSCM). A cooperative study of the Italian Association of Radiation Oncology (AIRO) Head and Neck Group.

BACKGROUND AND PURPOSE: Irradiation of the Pharyngeal Superior Constrictor Muscle (PSCM) seems to play a crucial role in radiation-related swallowing dysfunctions. Purpose of our study was to quantify operator-related variability in the contouring of PSCM on Computed Tomography (CT) scans and adherence with contours derived from MR images. MATERIALS AND METHODS: Three sets of treatment planning CT and their corresponding MR images were selected. Contouring of the PSCM was performed using both a literature-based method, derived from literature review, and an optimized method, derived from Magnetic Resonance (MR) images thus obtaining "literature-based" and "optimized" contours. Each operator contoured the PSCM on CT scans according to both methods for three times in three different days. Inter- and intra-operator variability and adherence to a contour obtained from MR images (named "MR-derived" contour) were analyzed. RESULTS: Thirty-four operators participated and 612 contours were obtained. Both intra- and inter-operator variability and adherence to the "MR-derived" contour were significantly different between the two methods (p⩽0.05). The "optimized" method showed a lower intra- and inter-operator variability and a higher adherence to the "MR-derived" contour. CONCLUSIONS: The "optimized" method ameliorates both operator-related variability and adherence with MR images.

Critical analysis of locoregional failures following intensity-modulated radiotherapy for nasopharyngeal carcinoma.

AIM: To analyze the patterns of locoregional failure following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) at our institution, as part of an internal quality assurance program. We aimed to investigate the potential existence of a correlation between any part of the IMRT process and clinical outcome. METHODS & MATERIALS: A total of 106 non-metastatic NPC patients consecutively treated with IMRT (with or without chemotherapy) were analyzed. Radiotherapy was administered using a sequential or simultaneous integrated boost approach at the total prescribed dose of 66-70 Gy (2.00-2.12 Gy per fraction). MRI studies of recurrences were recorded with the planning computed tomography studies to identify volume of failure. Recurrence-related characteristics were analyzed with respect to the original treatment. Failures were classified as 'in-field', 'marginal' or 'out-field' if at least 95, 20-95 or less than 20% of the volume of failure, respectively, was within 95% of the total prescription dose. RESULTS: With a median follow-up of 43.4 months, 5-years local control, regional control, locoregional control and overall survival rates were 87.7, 88.0, 83.5 and 81.3% respectively. A total of 21 failures were registered in 15 patients. In particular, ten failures (47.6%) were classified as 'in-field' (seven local failures and three regional failures [RFs]), nine failures (42.9%) as 'marginal' (five local failures and four RFs) and only two failures (9.5%) as 'out-field' (both RFs). The most relevant causes of failures were suboptimal target definition and target coverage as well as a longer than planned overall treatment time. CONCLUSION: IMRT determines excellent outcome in NPC patients. However, great attention in all IMRT steps is necessary to reduce potential causes of failure.

Preoperative intensified radiochemotherapy for rectal cancer: experience of a single institution.

PURPOSE: The aim of our study was to evaluate the feasibility and the effectiveness of an intensified neoadjuvant protocol with the addition of weekly oxaliplatin in the preoperative strategy of rectal cancer treatment. PATIENTS AND METHODS: Patients with locally advanced rectal cancer received continous infusion 5-Fluorouracil (5-FU) 200 mg/m(2)/day in combination with weekly oxaliplatin at a dose of 50 mg/m(2). Doses of radiotherapy were 45 Gy to the whole pelvis plus 5.4-9 Gy to the tumour mass. The primary end-points of the study were evaluation of toxicity, compliance with radiotherapy and chemotherapy, downstaging, pathological complete response (pCR) and the rate of sphincter preservation for distal cancers. Secondary end-points were relapse-free and overall survival. RESULTS: From November 2006 to June 2009, 51 patients were enrolled into the study. Compliance with chemotherapy was 80%. The incidence of G3 diarrhoea and proctitis were 17.6% and 21.5%, respectively. Surgery was performed in 48 patients with 100% R0 resection. 76.4% of low-lying tumours underwent conservative treatment. Seventy-nine percent of patients were downstaged: T and N downstaging were observed in 71% and 75% of patients, respectively. A pCR was obtained in 11 (22.9%) patients. CONCLUSIONS: Intensification of neoadjuvant treatment for rectal cancer with the addition of weekly oxaliplatin is feasible, with remarkable rates of downstaging and pathological complete response. Data on sphincter preservation for distal cancers were excellent. Phase III trials with a longer follow-up will establish whether this good outcome in terms of surrogate end-points will translate into better rates of disease-free and overall survival.

Chemoradiation as definitive treatment for primary squamous cell cancer of the rectum.

In this report, we present a case of advanced squamous cell cancer located in the rectum of a 78-year-old woman treated with chemoradiation with curative intent. The patient showed a complete clinical response to chemoradiation; multiple biopsies were performed at the site of the previous mass 5 mo after the end of treatment and histological examination showed no residual tumour in the specimens. Surgical intervention was avoided and the patient was free of disease 12 mo after the diagnosis of cancer. Primary chemoradiation should be considered as the treatment of choice for this rare malignancy.

Comparison between intensified neoadjuvant treatment and standard preoperative chemoradiation for rectal cancer.

OBJECTIVES: The aim of the current study was to compare a neoadjuvant regimen containing oxaliplatin with standard preoperative treatment for rectal cancer. METHODS: From December 2006 to December 2007, 20 patients with rectal cancer were treated at our Institution with the weekly addition of oxaliplatin (50 mg/m(2)) to radiotherapy (50.4-54.0 Gy in 28-30 daily fractions) and continuous infusion of 5-fluorouracil (200 mg/m(2)). The results of the regimen were compared with a historical control group including 21 consecutive patients previously treated with standard 5-fluorouracil treatment from December 2004 to October 2006. RESULTS: Both the rate of sphincter preservation in low rectal cancer (91.7% vs 36.4%, P = 0.009) and the rate of downstaging (84.2% vs 47.6%, P = 0.023) were higher in the oxaliplatin group than in the control group. Pathological complete response was achieved in 8 patients (42.1%) in the oxaliplatin group and in 4 patients (19.0%) in the control group (P = 0.172). When ypT0-pT1 stages were analyzed together, the P value was 0.051. Acute toxicity was increased in the oxaliplatin group, with a higher incidence of G3 diarrhea and pelvic pain than in the control group (30.0% vs 14.3%, P = NS). CONCLUSIONS: Our data seem to correlate the addition of oxaliplatin to the standard treatment for rectal cancer with higher rates of sphincter preservation, down-staging and complete response. Toxicity is increased and requires careful monitoring. However, our results refer to a retrospective comparison of a small series of patients and need to be validated by the large, phase III randomized trial currently ongoing.