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Introduction Few studies have systematically evaluated the risk of adverse events (AEs) among persons exercising during oncological treatment. We aimed to describe incidence and types of AEs during exercise for persons undergoing oncological treatment, and associations to exercise intensity, exercise adherence, chemotherapy treatment, initial aerobic fitness. A second aim was to compare incidence of lymphedema, periphery inserted central catheter (PICC) complications, and other new medical conditions (any illness or injury occurred during the exercise trial) between high-intensity vs low-to-moderate exercise and usual care (UC). Methods This descriptive, comparative study was based on data from an observational study including patients in an UC setting (n = 90) and a randomized exercise trial (n = 577) in which participants exercised at high-intensity (HI) or low-moderate intensity (LMI). Persons with breast, prostate, or colorectal cancer undergoing neo/adjuvant treatment were included. AEs were reported by exercise coaches, participants, and identified in medical records, as were lymphedema, PICC-complications, and new medical conditions. Results Coaches reported AEs for 20% of the participants, while 28% of participants self-reported AEs. The most common coach- and participant reported AEs were musculoskeletal and the majority (97%) were considered minor. HI had higher likelihood of AEs than LMI, according to both coaches (OR: 1.9 [95%CI 1.16-3.21], p=.011) and participants (OR: 3.36 [95%CI 2.00-5.62], ≤.001). Lymphedema rates were low (4-9%) and PICC complications ranged from 15% in LMI to 23% in UC and there were no statistically significant differences between HI, LMI, and UC. There were no statistically significant differences between HI and LMI regarding new medical conditions. Conclusions Exercise during treatment is safe for these patient groups in this setting, even HI exercise can be recommended if no medical contraindications are present. Similar to healthy populations, a higher risk of having minor AEs when exercising at HI in comparison to LMI may exist.

Squamous cell cancer of the anus is an uncommon malignancy, usually caused by human papilloma virus (HPV). Chemoradiotherapy (CRT) is the recommended treatment in localized disease with cure rates of 60-80%. Local failures should be considered for salvage surgery. With the purpose of improving and equalizing the anal cancer care in Sweden, a number of actions were taken between 2015 and 2017. The aim of this study was to describe the implementation of guidelines and organizational changes and to present early results from the first 5 years of the Swedish anal cancer registry (SACR).The following were implemented: (1) the first national care program with treatment guidelines, (2) standardized care process, (3) centralization of CRT to four centers and salvage surgery to two centers, (4) weekly national multidisciplinary team meetings where all new cases are discussed, (5) the Swedish anal cancer registry (SACR) was started in 2015.The SACR included 912 patients with a diagnosis of anal cancer from 2015 to 2019, reaching a national coverage of 95%. We could show that guidelines issued in 2017 regarding staging procedures and radiotherapy dose modifications were rapidly implemented. At baseline 52% of patients had lymph node metastases and 9% had distant metastases. Out of all patients in the SACR 89% were treated with curative intent, most of them with CRT, after which 92% achieved a local complete remission and the estimated overall 3-year survival was 85%.This is the first report from the SACR, demonstrating rapid nation-wide implementation of guidelines and apparently good treatment outcome in patients with anal cancer in Sweden. The SACR will hopefully be a valuable source for future research.

Background The Stockholm III trial randomly assigned 840 patients to short-course radiotherapy of 5 × 5 Gy with surgery within 1 week (SRT), short-course radiotherapy of 5 × 5 Gy with surgery after 4–8 weeks (SRT-delay), or long-course radiotherapy of 25 × 2 Gy with surgery after 4–8 weeks (LRT-delay). This study details the long-term oncological outcomes and health-related quality of life (HRQoL). Methods Patients with biopsy-proven resectable adenocarcinoma of the rectum were included. Primary outcome was time to local recurrence (LR), and secondary endpoints were distant metastases (DMs), overall survival (OS), recurrence-free survival (RFS), and HRQoL. Patients were analysed in a three-arm randomization and a short-course radiotherapy comparison. Results From 1998 to 2013, 357, 355, and 128 patients were randomized to the SRT, SRT-delay, and LRT-delay groups respectively. Median follow-up time was 5.7 (range 5.3–7.6) years. Comparing patients in the three-arm randomization, the incidence of LR was three of 129 patients, four of 128, and seven of 128, and DM 31 of 129 patients, 38 of 128, and 38 of 128 in the SRT, SRT-delay, and LRT-delay groups respectively. In the short-course radiotherapy comparison, the incidence of LR was 11 of 357 patients and 13 of 355, and DM 88 of 357 patients and 82 of 355 in the SRT and SRT-delay groups respectively. No comparisons showed statistically significant differences. Median OS was 8.1 (range 6.9–11.2), 10.3 (range 8.2–12.8), and 10.5 (range 7.0–11.3) years after SRT, SRT-delay, and LRT-delay respectively. Median OS was 8.1 (range 7.2–10.0) years after SRT and 10.2 (range 8.5–11.7) years after SRT-delay. There were no statistically significant differences in HRQoL. Conclusion After a follow-up of 5 years, delaying surgery for 4–8 weeks after radiotherapy treatment with 5 × 5 Gy was oncologically safe. Long-term HRQoL was similar among the treatment arms. Trial registration number NTC00904813, Analysis of long-term follow-up after radiotherapy and surgery for rectal cancer showed that delaying surgery for 4–8 weeks after radiotherapy treatment with 5 × 5 Gy seems oncologically safe. HRQoL does not seem to differ between treatment arms with radiotherapy and immediate surgery, compared with delayed surgery.

Summary Background Radiotherapy reduces the risk of local recurrence in rectal cancer. However, the optimal radiotherapy fractionation and interval between radiotherapy and surgery is still under debate. We aimed to study recurrence in patients randomised between three different radiotherapy regimens with respect to fractionation and time to surgery. Methods In this multicentre, randomised, non-blinded, phase 3, non-inferiority trial (Stockholm III), all patients with a biopsy-proven adenocarcinoma of the rectum, without signs of non-resectability or distant metastases, without severe cardiovascular comorbidity, and planned for an abdominal resection from 18 Swedish hospitals were eligible. Participants were randomly assigned with permuted blocks, stratified by participating centre, to receive either 5 × 5 Gy radiation dose with surgery within 1 week (short-course radiotherapy) or after 4–8 weeks (short-course radiotherapy with delay) or 25 × 2 Gy radiation dose with surgery after 4–8 weeks (long-course radiotherapy with delay). After a protocol amendment, randomisation could include all three treatments or just the two short-course radiotherapy treatments, per hospital preference. The primary endpoint was time to local recurrence calculated from the date of randomisation to the date of local recurrence. Comparisons between treatment groups were deemed non-inferior if the upper limit of a double-sided 90% CI for the hazard ratio (HR) did not exceed 1·7. Patients were analysed according to intention to treat for all endpoints. This study is registered with ClinicalTrials.gov, number NCT00904813. Findings Between Oct 5, 1998, and Jan 31, 2013, 840 patients were recruited and randomised; 385 patients in the three-arm randomisation, of whom 129 patients were randomly assigned to short-course radiotherapy, 128 to short-course radiotherapy with delay, and 128 to long-course radiotherapy with delay, and 455 patients in the two-arm randomisation, of whom 228 were randomly assigned to short-course radiotherapy and 227 to short-course radiotherapy with delay. In patients with any local recurrence, median time from date of randomisation to local recurrence in the pooled short-course radiotherapy comparison was 33·4 months (range 18·2–62·2) in the short-course radiotherapy group and 19·3 months (8·5–39·5) in the short-course radiotherapy with delay group. Median time to local recurrence in the long-course radiotherapy with delay group was 33·3 months (range 17·8–114·3). Cumulative incidence of local recurrence in the whole trial was eight of 357 patients who received short-course radiotherapy, ten of 355 who received short-course radiotherapy with delay, and seven of 128 who received long-course radiotherapy (HR vs short-course radiotherapy: short-course radiotherapy with delay 1·44 [95% CI 0·41–5·11]; long-course radiotherapy with delay 2·24 [0·71–7·10]; p=0·48; both deemed non-inferior). Acute radiation-induced toxicity was recorded in one patient ( vs short-course radiotherapy: short-course radiotherapy with delay 0·59 [95% CI 0·36–0·97], long-course radiotherapy with delay 0·63 [0·38–1·04], p=0·075). However, in a pooled analysis of the two short-course radiotherapy regimens, the risk of postoperative complications was significantly lower after short-course radiotherapy with delay than after short-course radiotherapy (144 [53%] of 355 vs 188 [41%] of 357; OR 0·61 [95% CI 0·45–0·83] p=0·001). Interpretation Delaying surgery after short-course radiotherapy gives similar oncological results compared with short-course radiotherapy with immediate surgery. Long-course radiotherapy with delay is similar to both short-course radiotherapy regimens, but prolongs the treatment time substantially. Although radiation-induced toxicity was seen after short-course radiotherapy with delay, postoperative complications were significantly reduced compared with short-course radiotherapy. Based on these findings, we suggest that short-course radiotherapy with delay to surgery is a useful alternative to conventional short-course radiotherapy with immediate surgery. Funding Swedish Research Council, Swedish Cancer Society, Stockholm Cancer Society, and the Regional Agreement on Medical Training and Clinical Research in Stockholm.

Few studies have systematically evaluated the risk of adverse events (AEs) among persons exercising during oncological treatment. We aimed to describe incidence and types of AEs during exercise for persons undergoing oncological treatment, and associations to exercise intensity, exercise adherence, chemotherapy treatment, initial aerobic fitness. A second aim was to compare incidence of lymphedema, periphery inserted central catheter (PICC) complications, and other new medical conditions (any illness or injury occurred during the exercise trial) between high-intensity vs low-to-moderate exercise and usual care (UC). This descriptive, comparative study was based on data from an observational study including patients in an UC setting (n = 90) and a randomized exercise trial (n = 577) in which participants exercised at high-intensity (HI) or low-moderate intensity (LMI). Persons with breast, prostate, or colorectal cancer undergoing neo/adjuvant treatment were included. AEs were reported by exercise coaches, participants, and identified in medical records, as were lymphedema, PICC-complications, and new medical conditions. Coaches reported AEs for 20% of the participants, while 28% of participants self-reported AEs. The most common coach- and participant reported AEs were musculoskeletal and the majority (97%) were considered minor. HI had higher likelihood of AEs than LMI, according to both coaches (OR: 1.9 [95%CI 1.16–3.21], p=.011) and participants (OR: 3.36 [95%CI 2.00–5.62], ≤.001). Lymphedema rates were low (4-9%) and PICC complications ranged from 15% in LMI to 23% in UC and there were no statistically significant differences between HI, LMI, and UC. There were no statistically significant differences between HI and LMI regarding new medical conditions. Exercise during treatment is safe for these patient groups in this setting, even HI exercise can be recommended if no medical contraindications are present. Similar to healthy populations, a higher risk of having minor AEs when exercising at HI in comparison to LMI may exist.

5-fluorouracil (5FU) and mitomycin C (MMC)-based chemoradiotherapy (CRT) is standard treatment for anal squamous cell carcinoma. In this phase I study cetuximab was added and the primary aim was to determine the maximum tolerated dose (MTD) of 5FU and MMC in this combination.Patients with locally advanced anal cancer, T2 (≥4 cm)-4N0-3M0, received weekly standard doses of cetuximab starting 1 week before CRT. Intensity modulated radiotherapy (IMRT) or volumetric modulated arc therapy (VMAT) with simultaneous integrated boost (SIB) was given to 57.5/54.0/48.6 Gy in 27 fractions to primary tumour/lymph node metastases/adjuvant lymph node regions. 5FU/MMC was given concomitantly on RT weeks 1 and 5 according to a predefined dose escalation schedule.Thirteen patients were enrolled. Two patients discontinued cetuximab due to hypersensitivity reaction. The median age was 65 years (range 46-70), nine were females, and 85% had stage IIIB disease. Dose-limiting toxicity events (diarrheoa, febrile neutropenia and thrombocytopenia) occurred in 3 of 11 patients. The most common grade 3-4 side-effects were radiation dermatitis (63%), haematologic toxicity (54%), and diarrheoa (36%). No treatment-related deaths occurred. Three months following completion of treatment, ten patients (91%) had a local complete remission (CR), but two patients had developed liver metastases, yielding a total CR rate of 73%.The MTDs were determined as 5FU 800 mg/m(2) on RT days 1-4 and 29-32 and MMC 8 mg/m(2) on days 1 and 29 when combined with IMRT/VMAT with SIB and cetuximab in locally advanced anal cancer.

In this paper we present a novel single-step RIE process for InP membrane optical waveguide etching. The optimization of the process is focused on the sidewall verticality and surface roughness of the etched profile. Significant improvement on the etched profile is achieved for the first time in a single-step RIE process. Loss measurement on fabricated membrane waveguides etched with the proposed RIE process results in a record low waveguide propagation loss (2.5 dB/cm).

Background To address issues regarding the fractionation of radiotherapy (RT) and timing of surgery for rectal cancer, a multicentre trial has randomized patients to preoperative short-course RT with two different intervals to surgery, or long-course RT with delayed surgery. The present interim analysis assessed feasibility, compliance and complications after RT and surgery. Methods Some 303 patients were randomized to either short-course RT (5 × 5 Gy) and surgery within 1 week (group 1), short-course RT and surgery after 4–8 weeks (group 2) or long-course RT (25 × 2 Gy) and surgery after 4–8 weeks (group 3). Results Demographic data were similar between groups and there were few protocol violations (5·0–6 per cent). Eight patients (2·6 per cent) developed radiation-induced acute toxicity. There were no significant differences in postoperative complications between groups (46·6, 40·0 and 32 per cent in groups 1, 2 and 3 respectively; P = 0·164). Patients receiving short-course RT with surgery 11–17 days after the start of RT had the highest complication rate (24 of 37). Conclusion Compliance was acceptable and severe acute toxicity was low, irrespective of fractionation. Short-course RT with immediate surgery had a tendency towards more postoperative complications, but only if surgery was delayed beyond 10 days after the start of RT. Registration number: NCT00904813 (http://www.clinicaltrials.gov).

Few studies have explored the potential clinical advantages of dose escalation and integrated boosts for patients with non-resectable locally advanced rectal cancer. The possibility of escalating dose to non-resectable regions in these patients was the aim of this study.Seven patients with locally very advanced rectal tumours (sacrum overgrowth or growth into pelvic side walls) were evaluated. Intensity modulated photon and pencil beam scanning proton plans with simultaneously integrated boosts (45 Gy to elective lymph nodes, 50 Gy to tumour and 62.5 Gy to boost area in 25 fractions) were compared.Target coverage was achieved with both photon and proton plans. Estimated risks of acute side effects put the two patients with the largest tumours at unacceptable risk for intestinal toxicity, regardless of modality. The remaining five patients had beneficial sparing of dose to the small intestine with protons.Adding boost to areas where rectal tumours infiltrate adjacent non-resectable organs is an attractive option which appears possible using both photon and proton irradiation. Proton plans reduced dose to organs at risk. Integrated peripheral boosts should be considered more frequently in these very advanced tumours.

Accurate delineation of target volumes is important to maximize radiation dose to the tumor and minimize it to nontumor tissue. Computed tomography (CT) and magnetic resonance imaging (MRI) are standard imaging modalities in rectal cancer. The aim was to explore whether functional imaging with F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET), combined with CT (FDG-PET/CT) gives additional information to standard pretreatment evaluation and changes the shape and size of the gross tumor volume (GTV).From 2007 to 2009, 77 consecutive patients with locally advanced rectal cancer were prospectively screened for inclusion in the study at two university hospitals in Sweden, and 68 patients were eligible. Standard GTV was delineated using information from clinical examination, CT, and MRI (GTV-MRI). Thereafter, a GTV-PET was defined in the fused PET-CT, and the target volume delineations were compared for total volume, overlap, and mismatch. Pathologic uptake suspect of metastases was also registered.The median volume of GTV-MRI was larger than that of GTV-PET: 111 cm(3) vs. 87 cm(3) (p0.001). In many cases, the GTV-MRI contained the GTV defined on the PET/CT images as subvolumes, but when a GTV total was calculated after the addition of GTV-PET to GTV-MRI, the volume increased, with median 11% (range, 0.5-72%). New lesions were seen in 15% of the patients for whom PET/CT was used.FDG-PET/CT facilitates and adds important information to the standard delineation procedure of locally advanced rectal cancer, mostly resulting in a smaller GTV, but a larger total GTV using the union of GTV-MRI and GTV-PET. New lesions were sometimes seen, potentially changing the treatment strategy.