SARS-CoV-2 vaccination willingness and humoral vaccination response in radiation oncology patients.

BACKGROUND: SARS-CoV-2 infection has been and, in some parts, still is a threat to oncologic patients, making it crucial to understand perception of vaccination and immunologic responses in this vulnerable patient segment. SARS-CoV-2 vaccines in relation to malignant disease characteristics and therapies have so far not been studied consecutively in larger oncologic patient populations. This study captures SARS-CoV-2 vaccination willingness and humoral immune response in a large consecutive oncologic patient collective at the beginning of 2021. METHODS: 1142 patients were consecutively recruited over 5.5 months at a tertiary department for radiation oncology and were assessed for vaccination willingness via a standardized interview. In already vaccinated patients total SARS-CoV-2 S antibody titres against the spike protein (Anti-SARS-CoV-2 S) and were evaluated 35 days or later after the first dose of SARS-CoV-2 vaccine. RESULTS: Vaccination willingness was high with a rate of 90 %. The most frequent reasons for rejection were: undecided/potential vaccination after therapy, distrust in the vaccine and fear of interaction with comorbidities. Factors associated with lower vaccination willingness were: worse general condition, lower age and female sex. 80 % of the participants had been previously vaccinated, 8 % reported previous infection and 16 % received vaccination during antineoplastic therapy. In 97.5 % of the vaccinated patients Anti-SARS-CoV-2 S was detected. In a univariable analysis parameters associated with non-conversion were: lower performance status, spread to the local lymphatics (N + ), hematologic disease and diffuse metastases. All patients with oligometastatic disease achieved positive Anti-SARS-CoV-2 S titres. For patients with two vaccinations several risk factors were identified, that were associated with low antibody concentrations. CONCLUSIONS: SARS-CoV-2 vaccination willingness among oncologic patients was high in the first months after its availability, and most patients had already received one or two doses. Over 97 % of vaccinated patients had measurable anti-SARS-CoV-2 S titres. Our data supports early identification of low humoral responders after vaccination and could facilitate the design of future oncologic vaccine trials (clinicaltrials.gov Identifier: NCT04918888).

Additional Value of 2-[18F]FDG PET/CT Comparing to MRI in Treatment Approach of Anal Cancer Patients.

Accurate staging and treatment planning are imperative for precise management in Anal Cancer (ACa) patients. We aimed to evaluate the additive and prognostic value of pre-treatment 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) in the staging and management of ACa compared to magnetic resonance imaging (MRI). This retrospective study was conducted on 54 patients. Pre-treatment 2-[18F]FDG PET/CT studies and MRI reports were compared considering the primary tumor, pelvic lymph nodes, and metastatic lesions. The impact of 2-[18F]FDG PET/CT in the management and its prognostic value, using maximum standardized uptake value (SUVmax), were assessed. Discordant findings were found in 46.3% of patients (5 in T; 1 in T and N; 18 in N; and 1 in M stage). 2-[18F]FDG PET/CT resulted in up-staging in 9.26% and down-staging in 3.7% of patients. Perirectal lymph nodes were metabolically inactive in 12.9% of patients. Moreover, 2-[18F]FDG PET/CT resulted in management change in 24.1% of patients. Finally, SUVmax provided no prognostic value. 2-[18F]FDG PET/CT altered staging and management in a sizable number of patients in this study, and supports a need for a change in guidelines for it to be used as a routine complementary test in the initial management of ACa.

Altered fractionation short-course radiotherapy for stage II-III rectal cancer: a retrospective study.

PURPOSE: To report the long-term outcomes of neoadjuvant altered fractionation short-course radiotherapy in 271 consecutive patients with stage II-III rectal cancer. PATIENTS AND METHODS: This was a retrospective single institution study with median follow-up of 101 months (8.4 years). Patients who were alive at the time of analysis in 2018 were contacted to obtain functional outcome data (phone interview). Radiotherapy consisted of 25 Gy in 10 fractions of 2.5 Gy administered twice daily. Median time interval to surgery was 5 days. RESULTS: Local relapse was observed in 12 patients (4.4%) after a median of 28 months. Overall survival after 5 and 10 years was 73 and 55.5%, respectively (corresponding disease-free survival 65.5 and 51%). Of all patients without permanent stoma, 79% reported no low anterior resection syndrome (LARS; 0-20 points), 9% reported LARS with 21-29 points and 12% serious LARS (30-42 points). CONCLUSION: The present radiotherapy regimen was feasible and resulted in low rates of local relapse. Most patients reported good functional outcomes.

Risk Factors for Local Relapse and Inferior Disease-free Survival After Breast-conserving Management of Breast Cancer: Recursive Partitioning Analysis of 2161 Patients.

BACKGROUND: The purpose of this study was to analyze risk factors for ipsilateral in-breast relapse and inferior disease-free survival (DFS) after standard adjuvant whole-breast radiotherapy (± boost and systemic treatment) as part of a multimodal breast-conserving approach. PATIENTS AND METHODS: Decision trees were built through recursive partitioning analysis (RPA). The median follow-up for all 2161 patients was 114 months (9.5 years). RESULTS: Local relapse in the treated breast was uncommon (actuarial rates after 5 and 10 years were 2.7% and 5.8%, respectively). In RPA, the first split was related to age (52 years), with younger patients having a significantly higher risk of local relapse. The younger patients were stratified further by lymph node ratio (LNR). In patients older than 52 years, lack of endocrine treatment was associated with significantly higher risk. DFS was 80.7% at 10 years. The first split was caused by LNR, and the group with unfavorable LNR (> 0.20) could not be stratified further. Ten-year DFS in this group was as low as 50.6%. Patients with favorable LNR (0-0.20) could be stratified by additional risk factors, in particular primary tumor size. CONCLUSION: RPA is a suitable method to assign patients with early stage breast cancer to different risk groups, both regarding local relapse and DFS. Although age was a major risk factor for local relapse after breast-conserving management, LNR was associated with both endpoints. The systemic treatment approaches used in this study failed to provide satisfactory DFS in patients with LNR > 0.20 and 2 other subgroups.

Total body irradiation with volumetric modulated arc therapy: Dosimetric data and first clinical experience.

BACKGROUND: To implement total body irradiation (TBI) using volumetric modulated arc therapy (VMAT). We applied the Varian RapidArc™ software to calculate and optimize the dose distribution. Emphasis was placed on applying a homogenous dose to the PTV and on reducing the dose to the lungs. METHODS: From July 2013 to July 2014 seven patients with leukaemia were planned and treated with a VMAT-based TBI-technique with photon energy of 6 MV. The overall planning target volume (PTV), comprising the whole body, had to be split into 8 segments with a subsequent multi-isocentric planning. In a first step a dose optimization of each single segment was performed. In a second step all these elements were calculated in one overall dose-plan, considering particular constraints and weighting factors, to achieve the final total body dose distribution. The quality assurance comprised the verification of the irradiation plans via ArcCheck™ (Sun Nuclear), followed by in vivo dosimetry via dosimeters (MOSFETs) on the patient. RESULTS: The time requirements for treatment planning were high: contouring took 5-6 h, optimization and dose calculation 25-30 h and quality assurance 6-8 h. The couch-time per fraction was 2 h on day one, decreasing to around 1.5 h for the following fractions, including patient information, time for arc positioning, patient positioning verification, mounting of the MOSFETs and irradiation. The mean lung dose was decreased to at least 80 % of the planned total body dose and in the central parts to 50 %. In two cases we additionally pursued a dose reduction of 30 to 50 % in a pre-irradiated brain and in renal insufficiency. All high dose areas were outside the lungs and other OARs. The planned dose was in line with the measured dose via MOSFETs: in the axilla the mean difference between calculated and measured dose was 3.6 % (range 1.1-6.8 %), and for the wrist/hip-inguinal region it was 4.3 % (range 1.1-8.1 %). CONCLUSION: TBI with VMAT provides the benefit of satisfactory dose distribution within the PTV, while selectively reducing the dose to the lungs and, if necessary, in other organs. Planning time, however, is extensive.

Medial tumor localization in breast cancer--an unappreciated risk factor?

PURPOSE: To demonstrate the unfavorable results in survival rates in patients with medial breast cancer compared to patients with laterally located tumors of the mammary gland. PATIENTS AND METHODS: Between 1984 and 1995, 1,089 patients presenting with a total of 1,100 pT1-2 invasive carcinomas of the breast were treated at the authors' institution. 707 presented with tumors in the lateral quadrants, 294 with tumors in the medial quadrants, and 99 with tumors in the central quadrant. Treatment protocols involved breast-conserving surgery and whole-breast radiotherapy in all women, followed by a tumor bed boost dose according to risk factors for local recurrence. All axillary node-positive patients underwent systemic therapy (six cycles of classic CMF and/or 2-5 years of tamoxifen 20 mg/day). Rates of actuarial survival and local control were calculated by the Kaplan-Meier method and differences in survival curves were compared by use of the log-rank test. RESULTS: The mean follow-up of survivors was 97 months (range 36-192 months). Comparing patients with medial and lateral tumors, the actuarial survival data were significantly better for patients with lateral tumors. At 10 years, overall survival for patients with medial tumors was 71%, for patients with lateral tumors 81.8% (p < 0.025), disease-specific survival for patients with medial tumors 79.9%, for patients with lateral tumors 89.1% (p < 0.025). There was no significant difference in local tumor control according to tumor location. CONCLUSION: Medial tumor location is associated with a lower survival rate, but not with inferior local tumor control. Failure to identify nodal metastases confined to the internal mammary chain may lead to undertreatment with systemic/local agents and compromised survival.

Local relapse after breast-conserving surgery and radiotherapy: effects on survival parameters.

PURPOSE: This retrospective analysis of 1,610 women treated for breast cancer and 88 patients with local relapse aims to show the poor survival parameters after local failure and to evaluate risk factors and compare them with other studies and analyses published. PATIENTS AND METHODS: Between 1984 and 1997, 1,610 patients presenting with a total of 1,635 pT1-2 invasive and noninvasive carcinomas of the breast were treated at the authors' institution. The mean age was 57.1 years (range 25-85 years). Treatment protocols involved breast-conserving surgery with or without systemic therapy and whole-breast radiotherapy in all women, followed by a boost dose to the tumor bed according to risk factors for local recurrence. All axillary node-positive patients underwent systemic therapy (six cycles of classic CMF or tamoxifen 20 mg/day for 2-5 years). The time of diagnosis of local relapse was defined as time 0 for the survival curves after local failure. The association of clinicopathologic factors was studied using uni- and multivariate analyses. Survival and local control were calculated by the Kaplan-Meier actuarial method and significance by the log-rank test. RESULTS: After a mean follow-up of 104 months, 88 local failures were recorded (5.4%). Calculated from the time of diagnosis of local relapse, 5-year overall survival (OS) was 62.8%, metastasis-free survival 60.6%, and disease-specific survival 64.2%. In patients with failure during the first 5 years after treatment, the survival parameters were worse (OS 50.6%) compared to those who relapsed after 5 years (OS 78.8%; p < 0.028). Significances were also found for initial T- and N-stage and type of failure (solid tumor vs. diffuse spread). CONCLUSION: This analysis again shows that the survival parameters are worsening after local relapse, especially in case of early occurrence. In breast cancer treatment, therefore, the goal remains to avoid local failure.