Incidence and Risk Assessment of Capsular Contracture in Breast Cancer Patients following Post-Mastectomy Radiotherapy and Implant-Based Reconstruction.

Our study aims to identify the risk factors and dosimetry characteristics associated with capsular contracture. METHODS: We retrospectively analyzed 118 women with breast cancer who underwent PMRT following an IBR between 2010 and 2022. Patients were treated with PMRT of 50.0-50.4 Gy in 25-28 fractions. Capsular contracture was categorized according to the Baker Classification for Reconstructed Breasts. RESULTS: After a median follow-up of 22 months, the incidence of clinically relevant capsular contracture (Baker III-IV) was 22.9%. Overall, capsular contracture (Baker I-IV) occurred in 56 patients (47.5%) after a median of 9 months after PMRT. The rate of reconstruction failure/implant loss was 25.4%. In the univariate analysis, postoperative complications (prolonged pain, prolonged wound healing, seroma and swelling) and regional nodal involvement were associated with higher rates of capsular contracture (p = 0.017, OR: 2.5, 95% CI: 1.2-5.3 and p = 0.031, respectively). None of the analyzed dosimetric factors or the implant position were associated with a higher risk for capsular contracture. CONCLUSION: Postoperative complications and regional nodal involvement were associated with an increased risk of capsular contracture following breast reconstruction and PMRT, while none of the analyzed dosimetric factors were linked to a higher incidence. Additional studies are needed to identify further potential risk factors.

Palliative Radiotherapy for Symptomatic Locally Advanced Breast Cancer.

Objective: Women with locally advanced breast cancer (LABC) or inoperable local recurrence often suffer from a significantly reduced quality of life (QOL) due to local tumor-associated pain, bleeding, exulceration, or malodorous discharge. We aimed to further investigate the benefit of radiotherapy (RT) for symptom relief while weighing the side-effects. Materials and methods: Patients who received symptom-oriented RT for palliative therapy of their LABC or local recurrence in the Department of Radiation Oncology at Heidelberg University Hospital between 2012 and 2021 were recorded. Clinical, pathological, and therapeutic data were collected and the oncological and symptomatic responses as well as therapy-associated toxicities were analyzed. Results: We retrospectively identified 26 consecutive women who received palliative RT with a median total dose of 39 Gy or single dose of 3 Gy in 13 fractions due to (impending) exulceration, pain, local hemorrhage, and/or vascular or plexus compression. With a median follow-up of 6.5 months after initiation of RT, overall survival at 6 and 12 months was 60.0% and 31.7%, and local control was 75.0% and 47.6%, respectively. Radiation had to be discontinued in 4 patients due to oncological clinical deterioration or death. When completed as initially planned, symptom improvement was achieved in 95% and WHO level reduction of analgesics in 28.6% of patients. In 36% (16%) of patients, local RT had already been indicated >3 months (>6 months) before the actual start of RT, but was delayed or not initiated among others in favor of drug alternatives or systemic therapies. RT-associated toxicities included only low-grade side-effects (CTCAE I°-II°) with predominantly skin erythema and fatigue even in the context of re-RT. Conclusion: Palliative RT in symptomatic LABC or locoregional recurrence is an effective treatment option for controlling local symptoms with only mild toxicity. It may thus improve QOL and should be considered early in palliative patient care management.

Dose-escalated re-irradiation improves outcome in locally recurrent head and neck cancer - Results of a large multicenter analysis.

To determine efficacy and prognostic parameters of definitive re-irradiation of locoregionally recurrent squamous cell carcinoma of the head and neck (HNSCC). MATERIALS AND METHODS: Patients with locoregionally recurrent or second primary HNSCC undergoing re-irradiation with modern radiotherapy technique were eligible for this multicentric retrospective analysis. Main endpoints were overall survival (OS), progression-free survival (PFS) and locoregional control (LC). Univariate analyses were performed using the Kaplan Meier Method (log-rank). For multivariable analysis, Cox regression was used. RESULTS: A total of 253 patients treated between 2009 and 2020 at 16 university hospitals in Germany were included. The median follow up was 27.4 months (range 0.5-130). The median OS and PFS were 13.2 (CI: 10.7 - 15.7) months and 7.9 (CI: 6.7 - 9.1) months, respectively, corresponding to two-year OS and PFS rates of 29 % and 19 %. Rates of locoregional progression and "in-field-failure" were 62 % and 51 % after two years. Multivariable Cox regression analysis identified good ECOG performance status and high radiation dose as independent prognostic parameters for OS. Doses above 50 Gy (EQD2) achieved longer median OS of 17.8 months (vs 11.7 months, p < 0.01) and longer PFS of 9.6 months (vs 6.8 months, p < 0.01). In addition, there was a trend for worse survival in patients with tracheostomy (multivariable, p = 0.061). Concomitant systemic therapy did not significantly impact PFS or OS. CONCLUSION: Re-irradiation of locally recurrent or second primary HNSCC is efficient, especially if doses above 50 Gy (EQD2) are delivered. ECOG performance score was the strongest prognostic parameter for OS and PFS.

Positron emission tomography (PET) in primary prostate cancer staging and risk assessment.

Prostate cancer (PCa) is one of the few neoplasms that are not well served by 18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET). As a result, a number of PET tracers have been developed to target particular biological features of PCa. Such agents can be used for diagnosis, staging, identification of biochemical recurrence (BCR) and evaluation of metastatic disease. Here, we focus on primary disease and local staging. To date, magnetic resonance imaging (MRI) has proven superior to PET in the imaging of primary PCa. However, some PET agents have shown remarkable promise in staging high-risk PCa (defined as any combination of a clinical T3, a PSA score >20 ng/mL, or a Gleason score of 8-10), as well as biochemical relapse after definitive therapy and metastatic PCa. PET agents can be divided into those that interrogate tumor metabolism (18F-FDG, 11C-Choline, 18F-Choline, 11C-Acetate, 18F-FACBC), hormone receptors (18F-FDHT), and other targets such as prostate specific membrane antigen (PSMA) (68Ga-PSMA, 18F-DCFBC, 18F-DCFPyl) or gastric releasing peptide (18F-GRP or 18F-Bombesin). In this review, we compare the available PCa targeted PET tracers utilized in staging of high risk tumors.

68Ga-PSMA PET/CT and Volumetric Morphology of PET-Positive Lymph Nodes Stratified by Tumor Differentiation of Prostate Cancer.

68Ga-prostate-specific membrane antigen (PSMA) PET/CT is a new method to detect early nodal metastases in patients with biochemical relapse of prostate cancer. In this retrospective investigation, the dimensions, volume, localization, and SUVmax of nodes identified by 68Ga-PSMA were correlated to their Gleason score (GS) at diagnosis. Methods: All PET/CT images were acquired 60 ± 10 min after intravenous injection of 68Ga-PSMA (mean dose, 176 MBq). In 147 prostate cancer patients (mean age, 68 y; range, 44-87 y) with prostate-specific antigen relapse (mean prostate-specific antigen level, 5 ng/mL; range, 0.25-294 ng/mL), 362 68Ga-PSMA PET-positive lymph nodes (LNs) were identified. These patients were classified on the basis of their histopathology at primary diagnosis into either low- (GS ≤ 6, well differentiated), intermediate- (GS = 7, moderately differentiated), or high-GS cohorts (GS ≥ 8, poorly differentiated prostate cancer). Using semiautomated LN segmentation software (Fraunhofer MEVIS), we measured node volume and short-axis dimensions (SADs) and long-axis dimensions based on CT and compared with the SUVmax Nodes demonstrating uptake of 68Ga-PSMA with an SUVmax of 2.0 or more were considered PSMA-positive, and nodes with an SAD of 8 mm or more were considered positive by morphologic criteria. Results: Mean SUVmax was 13.5 (95% confidence interval [CI], 10.9-16.1), 12.4 (95% CI, 9.9-14.9), and 17.8 (95% CI, 15.4-20.3) within the low-, intermediate-, and high-GS groups, respectively. The morphologic assessment of the 68Ga-PSMA-positive LN demonstrated that the low-GS cohort presented with smaller 68Ga-PSMA-positive LNs (mean SAD, 7.7 mm; n = 113), followed by intermediate- (mean SAD, 9.4 mm; n = 122) and high-GS cohorts (mean SAD, 9.5 mm; n = 127). On the basis of the CT morphology criteria, only 34% of low-GS patients, 56% of intermediate-GS patients, and 53% of high-GS patients were considered CT positive. Overall, 68Ga-PSMA imaging led to a reclassification of stage in 90 patients (61%) from cN0 to cN1 over CT. Conclusion:68Ga-PSMA PET is a promising modality in biochemical recurrent prostate cancer patients for N staging. Conventional imaging underestimates LN involvement compared with PSMA molecular staging score in each GS cohort. The sensitivity of 68Ga-PSMA PET/CT enables earlier detection of subcentimeter LN metastases in the biochemical recurrence setting.

Intraindividual Comparison of 18F-PSMA-1007 PET/CT, Multiparametric MRI, and Radical Prostatectomy Specimens in Patients with Primary Prostate Cancer: A Retrospective, Proof-of-Concept Study.

68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT represents an advanced method for the staging of primary prostate cancer (PCa) and diagnosis of recurrent or metastatic PCa. However, because of the narrow availability of 68Ga the development of alternative tracers is of high interest. The objective of this study was to examine the value of the new PET tracer 18F-PSMA-1007 for the staging of local disease by comparing it with multiparametric MRI (mpMRI) and radical prostatectomy (RP) histopathology. Methods: In 2016, 18F-PSMA-1007 PET/CT was performed in 10 men with biopsy-confirmed high-risk PCa. Nine patients underwent mpMRI in the process of primary diagnosis. Consecutively, RP was performed in all 10 men. Agreement analysis was performed retrospectively. PSMA staining was added for representative sections in RP specimen slices. Localization and agreement analysis of 18F-PSMA-1007 PET/CT, mpMRI, and RP specimens was performed by dividing the prostate into 38 sections as described in the prostate imaging reporting and data system (PI-RADS) (version 2). Sensitivity, specificity, positive predictive values, negative predictive values (NPVs), and accuracy were calculated for total and near-total agreement. Results:18F-PSMA-1007 PET/CT had an NPV of 68% and an accuracy of 75%, and mpMRI had an NPV of 88% and an accuracy of 73% for total agreement. Near-total agreement analysis resulted in an NPV of 91% and an accuracy of 93% for 18F-PSMA-1007 PET/CT and 91% and 87% for mpMRI, respectively. Retrospective combination of mpMRI and PET/CT had an accuracy of 81% for total and 93% for near-total agreement. Conclusion: Comparison with RP histopathology demonstrates that 18F-PSMA-1007 PET/CT is promising for accurate local staging of PCa.