Feasibility of a 12-month-exercise intervention during and after radiation and chemotherapy in cancer patients: impact on quality of life, peak oxygen consumption, and body composition

Background Accumulating evidence suggests that exercise is effective in treating many of the acute and chronic side effects of anti-cancer therapy. A recent meta-analysis supported the use of exercise to prevent or treat fatigue and lymphoedema and to improve functional status in breast cancer patients. Patients and methods This trial was intended as a controlled, prospective feasibility study evaluating the impact of physical exercise (PE) in cancer patients during and after treatment with radio- and chemotherapy. Inclusion criteria were previous or ongoing treatment for cancer, motivation for PE of 0.5-1hour duration at least twice weekly for at least 3 months. Continuation of PE was encouraged thereafter. Every three months the following endpoints were assessed: Peak oxygen consumption as measured by supervised cardiopulmonary exercise test, body composition and quality of life. Results A total of 45 patients were included with a median age of 49 years. Forty were female and five male. Cancer types were: Breast cancer (n = 30/67 %), gastrointestinal cancer (n = 5/12 %), other types (n = 10/22 %). Thirty-eight (84 %) of the patients were included during curative treatment of their disease. Seven (16 %) were considered palliative. Adherence to the PE-programme longer than 6 months was noted for 41/45 (91 %) of the patients. Intensity of PE was thrice weekly in 32/45 (71 %), twice weekly in 11/45 (24 %). Two of 45 patients (5 %) had no PE. Mean peak oxygen consumption increased from 18.8 ± 5.6 ml/min/kg to 20.5 ± 3 ml/min/kg and 19.9 ± 4.7 ml/min/kg at 3 months (p = 0.005) and 12 months (p = 0.003), respectively. Median fat mass decreased from 30.7 ± 15 kg to 28.9 ± 15 kg and 29.5 ± 13 kg at 3 months (p = 0.001) and 12 months (p = 0.017), respectively. Global health status scores increased from a median baseline value of 54.9 ± 16.3 to 66.4 ± 14 % and 68.0 ± 20.3 % at 3 months (p = 0.001) and 12 months (p = 0.002), respectively. Conclusion This exercise programme in cancer patients with 2–3 weekly supervised sessions over three months was well feasible and demonstrated measurable improvement of oxygen consumption, body composition and quality of life. In addition, a 90 %-adherence rate to the PE-programme beyond 6 months was encouraging. Further randomized prospective data in a larger patient population will be collected comparing the impact of two versus four months supervision

Distribution of immune cells in head and neck cancer: CD8+ T-cells and CD20+ B-cells in metastatic lymph nodes are associated with favourable outcome in patients with oro- and hypopharyngeal carcinoma

<p>Abstract</p> <p>Background</p> <p>Tumour infiltrating lymphocytes (TIL) are generally considered to represent a host immune response directed against tumour antigens. TIL are also increasingly recognised as possible prognostic parameters. However, the effects observed are variable indicating that results cannot be extrapolated from type of tumour to another. Moreover, it has been suggested that primary solid tumours may be ignored by the immune system and that a meaningful immune response is only mounted in regional lymph nodes.</p> <p>Methods</p> <p>We have examined the local distribution of immune cells in tumour-related compartments in head and neck squamous cell carcinomas (HNSCC). In a second step, the prognostic impact of these cells on disease-free survival (DFS) was analysed. A total of 198 tissue cores from 33 patients were evaluated using tissue mircroarray technique and immunohistochemistry. Tumour-infiltrating immune cells were identified using antibodies specific for CD3, CD8, GranzymeB, FoxP3, CD20 and CD68 and quantified using an image analysis system.</p> <p>Results</p> <p>We demonstrate a relative expansion of FoxP3⁺regulatory T-cells (Treg) and of cytotoxic T-cells among tumour infitrating T-cells. We also show that intratumoural CD20⁺B-cells are significantly more frequent in metastatic deposits than in primary tumours. Furthermore, we observed a reduced number of peritumoural CD8⁺T-cells in metastatic lymph nodes as compared to univolved regional nodes suggesting a local down-modulation of cellular immunity. All other immune cells did not show significant alterations in distribution. We did not observe an association of tumour infiltrating immune cells at the primary site with outcome. However, increased numbers of intraepithelial CD8⁺TIL in metastatic tumours as well as large numbers of peritumoural B-cells in lymph node metastases were associated with favourable outcome. Unexpectedly, no effect on patient outcome was observed for Treg in any compartment.</p> <p>Conclusion</p> <p>Our results suggest that alterations in lymphocyte distribution in regional lymph nodes rather than at the primary tumour site may be relevant for patient prognosis. Moreover, we demonstrate that in addition to cellular immunity humoral immune responses may be clinically relevant in anti-tumour immunity.</p

Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia

<p>Abstract</p> <p>Background</p> <p>Recent evidence suggests that CD4⁺CD25⁺FoxP3⁺regulatory T-cells (Treg) may be responsible for the failure of host anti-tumour immunity by suppressing cytotoxic T- cells. We assessed the prognostic significance of tumour infiltrating lymphocytes (TIL) in intestinal-type gastric cardiac cancer.</p> <p>Methods</p> <p>Tumour infiltrating lymphocyte (TIL) subsets and tumour infiltrating macrophages (TIM) were investigated in 52 cases using tissue microarrays. The interrelationship between the cell populations (CD3+, CD8+, CD20+, CD68+, GranzymeB+, FoxP3+) in different compartments and NED-survival was investigated (median follow-up time: 61 months).</p> <p>Results</p> <p>Intraepithelial infiltration with TIL and TIM including Treg was generally low and not related to NED-survival. However, patients with large numbers of FoxP3⁺Treg in the tumour stroma (>125.9 FoxP3⁺TILs/mm²) had a median survival time of 58 months while those with low FoxP3⁺TIL counts (<125.9 FoxP3⁺TILs/mm²) had a median survival time of 32 months (p = 0.006). Patients with high versus low stromal CD68⁺/FoxP3⁺cell ratios in primary tumour displayed median survivals of 32 and 55 months, respectively (p = 0.008).</p> <p>Conclusion</p> <p>Our results suggest that inflammatory processes within the tumour stroma of gastric intestinal-type adenocarcinomas located at the gastric cardia may affect outcome in two ways. Tumour-infiltrating macrophages are likely to promote carcinogenesis while large numbers of Treg are associated with improved outcome probably by inhibiting local inflammatory processes promoting carcinogenesis. Thus, inhibition of Treg may not be a feasible treatment option in gastric adenocarcinoma.</p

Primary resection versus neoadjuvant chemoradiation followed by resection for locally resectable or potentially resectable pancreatic carcinoma without distant metastasis. A multi-centre prospectively randomised phase II-study of the Interdisciplinary Working Group Gastrointestinal Tumours (AIO, ARO, and CAO)

BACKGROUND: The disappointing results of surgical therapy alone of ductal pancreatic cancer can only be improved using multimodal approaches. In contrast to adjuvant therapy, neoadjuvant chemoradiation is able to facilitate resectability with free margins and to lower lymphatic spread. Another advantage is better tolerability which consecutively allows applying multimodal treatment in a higher number of patients. Furthermore, the synopsis of the overall survival results of neoadjuvant trials suggests a higher rate compared to adjuvant trials. METHODS/DESIGN: As there are no prospectively randomised studies for neoadjuvant therapy, the Interdisciplinary Study Group of Gastrointestinal Tumours of the German Cancer Aid has started such a trial. The study investigates the effect of neoadjuvant chemoradiation in locally resectable or probably resectable cancer of the pancreatic head without distant metastasis on median overall survival time compared to primary surgery. Adjuvant chemotherapy is integrated into both arms. DISCUSSION: The protocol of the study is presented in condensed form after an introducing survey on adjuvant and neoadjuvant therapy in pancreatic cancer

Präoperative Radiotherapie plus Resektion vs. Operation allein bei Patienten mit primärem retroperitonealem Sarkom (EORTC-62092: STRASS): eine multizentrische, randomisierte Phase-III-Studie

Background!#!Emergency departments and emergency services are increasingly burdened by non-emergency patients. A substantial proportion of these is represented by older people. The project 'community emergency paramedic' ('Gemeindenotfallsanitäter' [G-NFS]) was initiated to prevent unnecessary use of emergency services.!##!Objective!#!To identify specific utilizations of the G‑NFS services by older people at home and in nursing homes.!##!Material and methods!#!Retrospective analysis of the assignment protocols from July 2019 through June 2020. Only data from patients aged ≥ 65 years were included. Data were grouped into whether patients lived on their own or in nursing homes.!##!Results!#!A total of 2358 protocols of older patients (mean age 80.8 years; 52.9% female) were evaluated and 55% of patients were treated on-site. The most frequently used measures by G‑NFS were counselling (79.4%), aid in self-medication (16.7%) and administration of medication (23.2%). Of the G‑NFS assignments 329 (14.0%) were carried out for nursing home residents. Measures related to urine catheter complications were more frequently performed in nursing home residents than in patients who lived at home (32.2% vs. 5.7%). Compared to other emergency cases, patients with catheter-related complications were most often treated at the scene (84.3% vs. 52.2%).!##!Conclusion!#!The G‑NFS enabled the majority of patients to be treated on-site, thus saving resources of emergency services and hospitals; however, the G‑NFS also performed measures that were normally the responsibility of general practitioners. This possibly highlights structural deficits in the medical and nursing care of older people

Left breast irradiation with tangential intensity modulated radiotherapy (t-IMRT) versus tangential volumetric modulated arc therapy (t-VMAT): trade-offs between secondary cancer induction risk and optimal target coverage

Background Adjuvant radiotherapy is the standard treatment after breast-conserving surgery. According to meta-analyses, adjuvant 3d-conventional irradiation reduces the risk of local recurrence and thereby improves long-term survival by 5–10%. However, there is an unintended exposure of organs such as the heart, lungs and contralateral breast. Irradiation of the left breast has been related to long-term effects like increased rates of coronary events as well as second cancer induction. Modern radiotherapy techniques such as tangential intensity modulated radiotherapy (t-IMRT) and tangential volumetric modulated arc therapy (t-VMAT) and particularly deep inspiration breath hold (DIBH) technique have been developed in order to improve coverage of target volume and to reduce dose to normal tissue. The aim of this study was to compare t-IMRT-plans with t-VMAT-plans in DIBH position for left-sided breast irradiation in terms of normal tissue exposure, i.e. of lungs, heart, left anterior descending coronary artery (LADCA), as well as homogeneity (HI) and conformity index (CI) and excess absolute risk (EAR) for second cancer induction for organs at risk (OAR) after irradiation. Methods Twenty patients, diagnosed with left-sided breast cancer and treated with breast-preserving surgery, were included in this planning study. For each patient DIBH-t-IMRT plan using 5 to 7 beams and t-VMAT plan using four rotations were generated to achieve 95% dose coverage to 95% of the volume. Data were evaluated on the basis of dose-volume histograms: Cardiac dose and LADCA (mean and maximum dose, D25% and D45%), dose to ipsilateral and contralateral lung (mean, D20%, D30%), dose to contralateral breast (mean dose), total monitor units, V5% of total body and normal tissue integral dose (NTID). In addition, homogeneity index and conformity index, as well as the excess absolute risk (EAR) to estimate the risk of second malignancy were calculated. Results T-IMRT showed a significant reduction in mean cardiac dose of 26% (p = 0.002) compared to t-VMAT, as well as a significant reduction in the mean dose to LADCA of 20% (p = 0.03). Following t-IMRT, mean dose to the left lung was increased by 5% (p = 0.006), whereas no significant difference was found in the mean dose to the right lung and contralateral breast between the two procedures. Monitor units were 31% (p = 0.000004) lower for t-IMRT than for t-VMAT. T-IMRT technique significantly reduced normal tissue integral dose (NTID) by 19% (p = 0.000005) and the V5% of total body by 24% (p = 0.0007). In contrast, t-VMAT improved CI and HI by 2% (p = 0.001) and 0.4% (p = 0.00001), respectively. EAR with t-IMRT was significantly lower, especially for contralateral lung and contralateral breast (2–5/10,000 person years) but not for ipsilateral lung. Conclusion Compared to t-VMAT, t-IMRT in left-sided breast irradiation significantly reduced dose to organs at risk as well as normal tissue integral dose, and V5% total body. EAR with t-IMRT was significantly lower for contralateral lung and contralateral breast. T-VMAT, however, achieved better homogeneity and conformity. This may be relevant in individual cases where sufficient coverage of medial lymphatic target volumes is warranted

Preoperative Radiochemotherapy in Rectal Cancer: Is There an Impact of Oxaliplatin on Pathologic Complete Response and Survival Rates under “Real World“ Conditions?

This study aimed to evaluate the benefit of additional administration of oxaliplatin during fluorouracil-based neoadjuvant radiochemotherapy (nRCT) in terms of pathologic complete remission (pCR), disease-free survival (DFS), and overall survival (OS) in patients with advanced rectal cancer. Between 2006 and 2021, 669 patients (pts) were diagnosed with locally advanced rectal cancer, of whom a total of 414 pts with nRCT were identified and included in the study. A total of 283 pts were treated by nRCT using concurrent chemotherapy with fluorouracil or capecitabine; 131 pts were treated using a combination of fluorouracil or capecitabine and oxaliplatin. Propensity score matching analyses (PSM) with 114 pts in each group were used to balance the patients’ characteristics. OS, DFS, pCR-rate, and potential prognostic factors were compared between the two groups. The median follow-up time was 59.5 weeks in the fluorouracil-group and 43 weeks in the fluorouracil/oxaliplatin group (p = 0.003). After PSM, the pCR-rate (including sustained clinical complete remission) was 27% (31/114 pts) in the fluorouracil/oxaliplatin group and 16% (18/114 pts) in the fluorouracil-group (p = 0.033). There was no difference between these two groups for both 10-year OS and DFS neither before nor after PSM, respectively (OS: 72.6% vs. 55.4%, p = 0.066, and 67.8% vs. 55.1%, p = 0.703, and DFS: 44.8% vs. 46.8%, p = 0.134, and 44.7% vs. 42.3%, p = 0.184). Multivariate analysis identified regression grading according to Dworak grade 4 (HR: 0.659; CI: 0.471–0.921; p = 0.015) and age over 60 years (HR: 2.231; CI: 1.245–4.001; p = 0.007) as independent predictors for OS. In conclusion, the addition of oxaliplatin to fluorouracil during nRCT significantly improved pCR-rate without having an impact on survival