Prognostic value of bone marrow and tumor 18 F-FDG uptake on PET/CT in patients with oropharyngeal cancer and the interplay between inflammation and FDG uptake.

AIMS: To examine the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) for disease recurrence and survival in patients with oropharyngeal squamous cell carcinoma (OP-SCC). The secondary aims were to evaluate the prognostic value of PET/CT parameters for the primary oropharyngeal tumor and total tumor burden, and to assess the correlation between FDG uptake variables and serum inflammatory markers. METHODS: This was an observational study of 91 patients with OP-SCC who underwent pretreatment FDG-PET/CT. The patients' blood samples were collected before treatment, and treatment was administered with the intention to cure. The median follow-up time was 40 months. The PET parameters measured were SUVmean BM for the assessment of BM FDG uptake, SUVmean , SUVmax , total lesion glycolysis (TLG), and metabolic tumor volume (MTV) for the evaluation of primary oropharyngeal tumor and total tumor burden. Blood samples were analyzed to determine each patient's white cell, red cell, and platelet cell counts, hemoglobin, and C-reactive protein level. In a subgroup of 33 patients, blood serum was analyzed to evaluate the expression of serum immune proteins using a proximity extension assay (Olink Proteomics). RESULTS: The univariate analysis revealed that SUVmean BM and tumor-specific parameters (SUVmax tumor, SUVmean total, SUVmax total, MTVtotal, TLGtotal) were significantly associated with recurrence-free survival (RFS). After adjusting for age, sex, and stage only SUVmean BM remained significantly associated with RFS. Spearman's correlation identified several correlations between PET parameters and inflammatory markers. CONCLUSIONS: Our results show that several FDG-PET/CT parameters may have a prognostic value of treatment outcome in patients with OP-SCC. However, SUVmean BM was the only independent PET parameter that showed a prognostic value for RFS in the study cohort. Moreover, the study findings might suggest an association between systemic inflammation and the metabolic activity in the BM.

The role of serum thymidine kinase 1 activity in neoadjuvant-treated HER2-positive breast cancer: biomarker analysis from the Swedish phase II randomized PREDIX HER2 trial.

BACKGROUND: Thymidine kinase 1 (TK1) plays a pivotal role in DNA synthesis and cellular proliferation. TK1 has been studied as a prognostic marker and as an early indicator of treatment response in human epidermal growth factor 2 (HER2)-negative early and metastatic breast cancer (BC). However, the prognostic and predictive value of serial TK1 activity in HER2-positive BC remains unknown. METHODS: In the PREDIX HER2 trial, 197 HER2-positive BC patients were randomized to neoadjuvant trastuzumab, pertuzumab, and docetaxel (DPH) or trastuzumab emtansine (T-DM1), followed by surgery and adjuvant epirubicin and cyclophosphamide. Serum samples were prospectively collected from all participants at multiple timepoints: at baseline, after cycle 1, 2, 4, and 6, at end of adjuvant therapy, annually for a total period of 5 years and/or at the time of recurrence. The associations of sTK1 activity with baseline characteristics, pathologic complete response (pCR), event-free survival (EFS), and disease-free survival (DFS) were evaluated. RESULTS: No association was detected between baseline sTK1 levels and all the baseline clinicopathologic characteristics. An increase of TK1 activity from baseline to cycle 2 was seen in all cases. sTK1 level at baseline, after 2 and 4 cycles was not associated with pCR status. After a median follow-up of 58 months, 23 patients had EFS events. There was no significant effect between baseline or cycle 2 sTK1 activity and time to event. A non-significant trend was noted among patents with residual disease (non-pCR) and high sTK1 activity at the end of treatment visit, indicating a potentially worse long-term prognosis. CONCLUSION: sTK1 activity increased following neoadjuvant therapy for HER2-positive BC but was not associated with patient outcomes or treatment benefit. However, the post-surgery prognostic value in patients that have not attained pCR warrants further investigation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02568839. Registered on 6 October 2015.

Comparison between Swedish EORTC QLQ-C30 general population norm data published in 2000 and 2019.

BACKGROUND: Normative health-related quality of life (HRQoL) data from the general population are regularly used to facilitate the interpretation of HRQoL as reported by cancer patients participating in cancer clinical trials, especially when conducting long-term follow-up studies after treatment. The aim of the present study is to compare two Swedish normative data sets, published in 2000 and 2019 respectively, and explore whether HRQoL as reported by the Swedish general population has changed over time. MATERIAL AND METHODS: 'Sample 2000' was comprised of normative data from the Swedish general population who responded to the EORTC QLQ-C30 in a Swedish mail survey in 1999 (n = 3069). 'Sample 2019' consisted of data from the Swedish general population collected as part of a European norm data study using online panels, published in 2019 (n = 1027). Data were analyzed stratified by sex and age (40-49; 50-59; 60-69; 70-79 years). RESULTS: For most of the subscales and single items, no age group differences between the two samples were found, with the exception of the oldest age group (70-79 years), where Sample 2019 generally showed better HRQoL as compared to Sample 2000. Lower (worse) levels of Global quality of life and higher (worse) levels of Dyspnoea were found in Sample 2019 for most age groups. CONCLUSION: There were no differences found between the samples for most EORTC QLQ-C30 subscales and single items, with the exception of the oldest age group of both sexes in Sample 2019 who reported better HRQoL on many variables. When deciding which normative dataset to use, the mode of data collection and age group have to be considered.

Incidence of and survival after surgical intervention for bowel obstruction in women with advanced ovarian cancer.

INTRODUCTION: Women with advanced ovarian cancer commonly present with peritoneal disease both at primary diagnosis and relapse, with risk of subsequent bowel obstruction. The aims of this study were to assess the cumulative incidence of and survival after intervention for bowel obstruction in women with advanced ovarian cancer, to identify factors predictive of survival and the extent to which the intended outcome of the intervention was achieved. MATERIAL AND METHODS: Women diagnosed with advanced ovarian cancer stages III and IV in 2009-2011 and 2014-2016 in the Stockholm-Gotland Region in Sweden were identified in the Swedish Quality Registry for Gynecologic Cancer. Through hospital records, types of intended and executed interventions for bowel obstruction were assessed, and as well as when in the course of oncologic treatment, the intervention was performed. Time from first intervention to death was analyzed with survival methodology and proportional hazard regression was used. RESULTS: Of 751 identified women, 108 had an intervention for bowel obstruction. Laparotomy was the most prevalent intervention and was used in 87% (94/108) of all women, with a success rate of 87% (82/94). An intervention for bowel obstruction was performed before or during first line treatment in 32% (35/108) with a cumulative incidence in the whole cohort of 14% (108/751, 95% confidence interval [CI] 11-16). Median survival after intervention for bowel obstruction was 4 months (95% CI 3-6). The hazard of death increased when the intervention was performed after completion of primary treatment (HR 4.46, 95% CI 1.61-12.29, P < 0.01), with a median survival of 3 months. In women subjected to radical surgery during primary treatment, the hazard of death after intervention for bowel obstruction decreased (hazard ratio [HR] 0.54, 95% CI 0.32-0.91, P = 0.02). CONCLUSIONS: Women with advanced ovarian cancer undergoing intervention for bowel obstruction have a dismal prognosis, regardless of which line of oncologic treatment the intervention was performed. In the majority of women an intervention for bowel obstruction was performed in a relapse situation with an even worse survival. Our findings emphasize the importance of a holistic approach in the decision-making before an intervention for bowel obstruction in women with advanced ovarian cancer.

Incidence of cardiovascular and bleeding events and reasons for discontinuation in patients with chronic lymphocytic leukemia treated with ibrutinib-A retrospective analysis on consecutive patients from a well-defined region.

OBJECTIVE: Ibrutinib treatment is associated with cardiovascular side effects, in particular atrial fibrillation (AF) and hypertension, as well as increased risk of bleeding. Here, we aimed at describing the incidence of these events during long-term follow-up in patients with chronic lymphocytic leukemia treated outside clinical trials as well as identifying clinical factors predictive of developing AF. Additionally, other reasons for treatment withdrawal were analyzed. METHODS: The study was retrospective, data were collected from medical records. RESULTS: A total of 134 patients were identified. Median follow-up was 32 months (range 3-103) and median duration of ibrutinib treatment was 26 months (range 1-103). Of 110 patients with no prior history of AF, 24.5% were diagnosed during treatment. Newly diagnosed or worsening of pre-existing hypertension occurred in 15.7%. Sixty-six % of the patients experienced bleeding events, of which 7.5% grade 3-4. Treatment discontinuation and dose reduction occurred in 68% and 47% of the patients, respectively, mostly due to toxicity. CONCLUSIONS: The incidence of AF was high and at a median follow-up of 2.5 years, two-thirds of the patients discontinued treatment mostly due to bleeding and infections. Treatment-related toxicity of any grade should be regarded as a concern of prolonged ibrutinib therapy.

Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia: A Swedish nation-wide real-world report on consecutively identified patients.

OBJECTIVES: We examined the efficacy and toxicity of the PI3Kδ inhibitor idelalisib in combination with rituximab salvage therapy in consecutively identified Swedish patients with chronic lymphocytic leukemia (CLL). METHODS AND RESULTS: Thirty-seven patients with relapsed/refractory disease were included. The median number of prior lines of therapy was 3 (range 1-11); the median age was 69 years (range 50-89); 22% had Cumulative Illness Rating Scale (CIRS) >6 and 51% had del(17p)/TP53 mutation. The overall response rate was 65% (all but one was partial response [PR]). The median duration of therapy was 9.8 months (range 0.9-44.8). The median progression-free survival was 16.4 months (95% CI: 10.4-26.3) and median overall survival had not been reached (75% remained alive at 24 months of follow-up). The most common reason for cessation of therapy was colitis (n = 8, of which seven patients experienced grade ≥3 colitis). The most common serious adverse event was grade ≥3 infection, which occurred in 24 patients (65%). CONCLUSIONS: Our real-world results suggest that idelalisib is an effective and relatively safe treatment for patients with advanced-stage CLL when no other therapies exist. Alternative dosing regimens and new PI3K inhibitors should be explored, particularly in patients who are double-refractory to inhibitors of BTK and Bcl-2.

OptiBra study, a randomized controlled trial on optimal postoperative bra support after breast cancer surgery.

AIM: This randomized controlled trial aimed to compare two different postoperative bras after breast cancer surgery and evaluate their impact on primary outcome pain. METHOD: The study included 201 patients scheduled for primary surgery (breast conserving surgery with sentinel node biopsy or axillary clearance, mastectomy, or mastectomy with primary implant reconstruction with sentinel node biopsy or axillary clearance). Participants were randomized to either a soft bra or stable bra with compression. The patients were recommended to use the bra 24 h/day for 3 weeks, record daily pain (NRS), analgesic use and hours of bra use. RESULTS: Follow up was completed by 184 patients. No significant differences between the arms were found considering pain score over time, neither day 1-14, nor after 3 weeks. Sixty-eight percent of all patients, regardless of randomization, reported pain during the first 14 days. After 3 weeks 46% still reported pain in the operated breast. Among these, patients randomized to the stable bra with compression reported significantly lower pain score than those randomized to the soft bra. Patients who used the stable bra with compression reported significantly higher levels of comfort, sense of security during activity, less difficulty moving the arm, as well as support and stability for the operated breast compared to those using the soft bra. CONCLUSION: Using a stable bra with compression is the optimal evidence-based choice after breast cancer surgery to reduce remaining pain 3 weeks after surgery, increasing mobility, comfort, and sense of security. TRIAL REGISTRATION NUMBER: NCT04059835 at www. CLINICALTRIALS: gov.

Survival and chance of reversal after intestinal stoma formation during cytoreductive surgery for advanced ovarian cancer; a population-based cohort study.

OBJECTIVE: Our objective was to examine oncologic outcome in women with advanced epithelial ovarian cancer (aEOC) receiving an intestinal stoma (IS) at the time of cytoreductive surgery (CRS), probability of stoma reversal (SR) and variables affecting odds of SR. METHODS: This population-based cohort study included all women diagnosed with aEOC between 2009 and 2018 in the Stockholm/Gotland Region of Sweden. The association between IS formation at CRS and survival was analyzed with proportional hazards regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for predefined confounders. Cumulative incidence functions, with death or recurrence as competing risk, were used to estimate chance of SR. The association between clinical factors and SR was analyzed with logistic regression yielding odds ratios (OR) with 95% CI. RESULTS: The final analysis included 888 women undergoing CRS for aEOC. Of these, 129 (14,5%) received an IS of which 74% (n = 95) were defunctioning and 26% (n = 34) permanent. IS was associated with an increased hazard of death (HR 1.30, CI 95%, 1.05-1.61; p = 0.02) in the univariate analysis, however not in the adjusted analysis. The probability of SR of defunctioning IS within 2 years was 48% (95% CI, 38-58). Median time to SR was 10 months. High surgical complexity score (SCS) was associated with increased odds of reversal (OR 3.43, 95% CI, 1.06-11.05; p = 0.04). CONCLUSIONS: IS formation does not seem to affect prognosis in women with aEOC. We could not identify any factor, known at time of CRS, that may predict the odds of SR except a high SCS.

Loco-Regional Control and Sustained Difference in Serum Immune Protein Expression in Patients Treated for p16-Positive and p16-Negative Head and Neck Squamous Cell Carcinoma.

The main prognostic factors for patients with head and neck cancer are the tumour site and stage, yet immunological and metabolic factors are certainly important, although knowledge is still limited. Expression of the biomarker p16INK4a (p16) in oropharyngeal cancer tumour tissue is one of the few biomarkers for the diagnosis and prognosis of head and neck cancer. The association between p16 expression in the tumour and the systemic immune response in the blood compartment has not been established. This study aimed to assess whether there is a difference in serum immune protein expression profiles between patients with p16+ and p16- head and squamous cell carcinoma (HNCC). The serum immune protein expression profiles, using the Olink® immunoassay, of 132 patients with p16+ and p16- tumours were compared before treatment and one year after treatment. A significant difference in the serum immune protein expression profile was observed both before and one year after treatment. In the p16- group, a low expression of four proteins: IL12RB1, CD28, CCL3, and GZMA before treatment conferred a higher rate of failure. Based on the sustained difference between serum immune proteins, we hypothesise that the immunological system is still adapted to the tumour p16 status one year after tumour eradication or that a fundamental difference exists in the immunological system between patients with p16+ and p16- tumours.

Whole-body MRI surveillance in TP53 carriers is perceived as beneficial with no increase in cancer worry regardless of previous cancer: Data from the Swedish TP53 Study.

BACKGROUND: To evaluate the psychosocial consequences of surveillance with whole-body MRI (WB-MRI) in individuals with the heritable TP53-related cancer (hTP53rc) syndrome, also known as the Li-Fraumeni syndrome, with regard to cancer worry, perceived benefits and risks to surveillance and overall health. PATIENTS AND METHODS: Since 2016, the national Swedish TP53 Study (SWEP53) has offered surveillance with WB-MRI to all individuals with hTP53rc syndrome. Seventy-five individuals have been included in the study. Sixty consecutive participants fulfilled a base-line evaluation as well as an evaluation after 1 year with structured questionnaires including the Cancer Worry Scale (CWS), perceived benefits and risks of surveillance, and the 36-item Short Form Survey (SF-36). Individuals with or without previous personal cancer diagnosis were enrolled and results at baseline and after 1 year of surveillance were compared. For SF-36, a comparison with the normal population was also made. RESULTS: Participants with previous cancer tend to worry more about cancer, but both individuals with and without cancer had a positive attitude toward surveillance with no differences regarding perceived benefits and barriers to surveillance. Participants with a previous cancer scored significantly lower on some of the SF-36 subscales, but between-group differences were found only for social functioning after 1 year. CONCLUSIONS: Surveillance with WB-MRI is feasible from a psychosocial point of view both among TP53 carriers with as well as without a previous history of cancer and does not increase cancer worry in any of the groups. PLAIN LANGUAGE SUMMARY: Individuals with heritable TP53-related cancer syndrome (also known as the Li-Fraumeni syndrome) have a high lifetime risk of developing cancer. These TP53 carriers are offered surveillance with whole-body MRI to detect cancer early. There are few reports of the psychosocial impact of surveillance. In this study, we wanted to evaluate cancer worry, benefits and barriers to participation, and perceived overall health. Our study shows no increase in cancer worry after 1 year of surveillance, regardless of previous cancer.

Survival Outcomes, Digital TILs, and On-treatment PET/CT During Neoadjuvant Therapy for HER2-positive Breast Cancer: Results from the Randomized PREDIX HER2 Trial.

PURPOSE: PREDIX HER2 is a randomized Phase II trial that compared neoadjuvant docetaxel, trastuzumab, and pertuzumab (THP) with trastuzumab emtansine (T-DM1) for HER2-positive breast cancer. Rates of pathologic complete response (pCR) did not differ between the two groups. Here, we present the survival outcomes from PREDIX HER2 and investigate metabolic response and tumor-infiltrating lymphocytes (TIL) as prognostic factors. PATIENTS AND METHODS: In total, 202 patients with HER2-positive breast cancer were enrolled and 197 patients received six cycles of either THP or T-DM1. Secondary endpoints included event-free survival (EFS), recurrence-free survival (RFS), and overall survival (OS). Assessment with PET/CT was performed at baseline, after two and six treatment cycles. TILs were assessed manually at baseline biopsies, while image-based evaluation of TILs [digital TILs (DTIL)] was performed in digitized full-face sections. RESULTS: After a median follow-up of 5.21 years, there was no difference between the two treatment groups in terms of EFS [HR = 1.26; 95% confidence interval (CI), 0.54-2.91], RFS (HR = 0.69; 95% CI, 0.24-1.93), or OS (HR = 0.52; 95% CI, 0.09-2.82). Higher SUVmax at cycle 2 (C2) predicted lower pCR (ORadj = 0.65; 95% CI, 0.48-0.87; P = 0.005) and worse EFS (HRadj = 1.27; 95% CI, 1.12-1.41; P < 0.001). Baseline TILs and DTILs provided additional prognostic information to clinical parameters and C2 SUVmax. CONCLUSIONS: Long-term outcomes following neoadjuvant T-DM1 were similar to neoadjuvant THP. SUVmax after two cycles of neoadjuvant therapy for HER2-positive breast cancer may be an independent predictor of both short- and long-term outcomes. Combined assessment with TILs may facilitate early selection of poor responders for alternative treatment strategies.

Clinical assessment of breast symmetry and aesthetic outcome: can 3D imaging be the gold standard?

There is a lack of an accurate standardised objective method to assess aesthetic outcome after breast surgery. In this methodological study, we investigated the intra- and inter-observer reproducibility of breast symmetry and volume assessed using three-dimensional surface imaging (3D-SI), evaluated the reproducibility depending on imaging posture, and proposed a new combined volume-shape-symmetry (VSS) parameter. Images were acquired using the VECTRA XT 3D imaging system, and analysed by two observers using VECTRA Analysis Module. Breast symmetry was measured through the root mean square distance. All women had undergone bilateral risk-reducing mastectomy and immediate breast reconstruction. The reproducibility and correlations of breast symmetry and volume measurements were compared using Bland-Altman's plots and tested with Spearman's rank correlation coefficient. 3D surface images of 58 women were analysed (348 symmetry measurements, 696 volume measurements). The intra-observer reproducibility of breast symmetry measurements was substantial-excellent, the inter-observer reproducibility was substantial, and the inter-posture reproducibility was substantial. For measurements of breast volumes, the intra-observer reproducibility was excellent, the inter-observer reproducibility was moderate-substantial, and the inter-posture reproducibility was substantial-excellent. The intra-observer reproducibility of VSS was excellent while the inter-observer reproducibility was substantial for both observers, independent of posture. There were no statistically strong correlations between breast symmetry and volume differences. The intra-observer reproducibility was found to be substantial-excellent for several 3D-SI measurements independent of imaging posture. However, the inter-observer reproducibility was lower than the intra-observer reproducibility, indicating that 3D-SI in its present form is not a great assessment for symmetry.

High levels of health-related quality of life five years after curative treatment of prostate cancer with HDR-brachytherapy and external beam radiation.

BACKGROUND AND PURPOSE: The aim of this cross-sectional study was to investigate long-term health-related quality of life (HRQoL) in men with prostate cancer treated 2002-2008 with external beam radiotherapy (EBRT) combined with high dose-rate brachytherapy (HDRBT), Cohort A, and to compare these data with age-adjusted normative data. In addition, differences in HRQoL following adjustments of the brachytherapy technique in 2001 were investigated by comparing Cohort A with men treated at the same clinic from 1998-2000, Cohort B. METHODS AND MATERIAL: Cohort A: 1495 men treated with EBRT 2 Gy to 50 Gy and 2 fractions of 10 Gy HDRBT at a single centre, 2002-2008, still alive at five years. As part of routine follow-up, the patients responded to the EORTC QLQ-C30 and PR-25 questionnaires. Cohort B: HRQoL data was retrieved from an earlier study from the original article. RESULTS: In Cohort A, 1046 (70%) men completed the questionnaires at five years, median age 66 years. In general, HRQoL mean scores were high and similar to Swedish age-matched normative data. Concerning disease-specific HRQoL, low levels of bowel and urinary problems were reported, in contrast to a substantial effect on sexual functioning. 'No' or 'A little' problems with faecal incontinence and urinary incontinence were reported by 98% and 93% of patients, respectively. The corresponding figure for sexual functioning was 39%. A difference in the frequency of nocturia in favour of Cohort A was the only statistically significant difference between Cohort A and B found in general and disease-specific HRQOL (p = 0.03), despite modifications in the brachytherapy procedure introduced in 2001. CONCLUSION: Long-term general HRQoL was rated high and comparable to an aged-matched reference population five years after treatment with combined radiotherapy. Disease-specific HRQoL was still affected, foremost in the sexual domain.

Effectiveness of Single vs Multiple Doses of Prophylactic Intravenous Antibiotics in Implant-Based Breast Reconstruction: A Randomized Clinical Trial.

Importance: Multiple-dose antibiotic prophylaxis is widely used to prevent infection after implant-based breast reconstruction despite the lack of high-level evidence regarding its clinical benefit. Objective: To determine whether multiple-dose antibiotic prophylaxis is superior to single-dose antibiotic prophylaxis in preventing surgical site infection (SSI) after implant-based breast reconstruction. Design, Setting, and Participants: This prospective, multicenter, randomized clinical superiority trial was conducted at 7 hospitals (8 departments) in Sweden from April 25, 2013, to October 31, 2018. Eligible participants were women aged 18 years or older who were planned to undergo immediate or delayed implant-based breast reconstruction. Follow-up time was 12 months. Data analysis was performed from May to October 2021. Interventions: Multiple-dose intravenous antibiotic prophylaxis extending over 24 hours following surgery, compared with single-dose intravenous antibiotic. The first-choice drug was cloxacillin (2 g per dose). Clindamycin was used (600 mg per dose) for patients with penicillin allergy. Main Outcomes and Measures: The primary outcome was SSI leading to surgical removal of the implant within 6 months after surgery. Secondary outcomes were the rate of SSIs necessitating readmission and administration of intravenous antibiotics, and clinically suspected SSIs not necessitating readmission but oral antibiotics. Results: A total of 711 women were assessed for eligibility, and 698 were randomized (345 to single-dose and 353 to multiple-dose antibiotics). The median (range) age was 47 (19-78) years for those in the multiple-dose group and 46 (25-76) years for those in the single-dose group. The median (range) body mass index was 23 (18-38) for the single-dose group and 23 (17-37) for the multiple-dose group. Within 6 months of follow-up, 30 patients (4.3%) had their implant removed because of SSI. Readmission for intravenous antibiotics because of SSI occurred in 47 patients (7.0%), and 190 women (27.7%) received oral antibiotics because of clinically suspected SSI. There was no significant difference between the randomization groups for the primary outcome implant removal (odds ratio [OR], 1.26; 95% CI, 0.69-2.65; P = .53), or for the secondary outcomes readmission for intravenous antibiotics (OR, 1.18; 95% CI, 0.65-2.15; P = .58) and prescription of oral antibiotics (OR, 0.72; 95% CI, 0.51-1.02; P = .07). Adverse events associated with antibiotic treatment were more common in the multiple-dose group than in the single-dose group (16.4% [58 patients] vs 10.7% [37 patients]; OR, 1.64; 95% CI, 1.05-2.55; P = .03). Conclusions and Relevance: The findings of this randomized clinical trial suggest that multiple-dose antibiotic prophylaxis is not superior to a single-dose regimen in preventing SSI and implant removal after implant-based breast reconstruction but comes with a higher risk of adverse events associated with antibiotic treatment. Trial Registration: EudraCT 2012-004878-26.

Neoadjuvant Chemoradiotherapy and Surgery for Esophageal Squamous Cell Carcinoma Versus Definitive Chemoradiotherapy With Salvage Surgery as Needed: The Study Protocol for the Randomized Controlled NEEDS Trial.

Background: The globally dominant treatment with curative intent for locally advanced esophageal squamous cell carcinoma (ESCC) is neoadjuvant chemoradiotherapy (nCRT) with subsequent esophagectomy. This multimodal treatment leads to around 60% overall 5-year survival, yet with impaired post-surgical quality of life. Observational studies indicate that curatively intended chemoradiotherapy, so-called definitive chemoradiotherapy (dCRT) followed by surveillance of the primary tumor site and regional lymph node stations and surgery only when needed to ensure local tumor control, may lead to similar survival as nCRT with surgery, but with considerably less impairment of quality of life. This trial aims to demonstrate that dCRT, with selectively performed salvage esophagectomy only when needed to achieve locoregional tumor control, is non-inferior regarding overall survival, and superior regarding health-related quality of life (HRQOL), compared to nCRT followed by mandatory surgery, in patients with operable, locally advanced ESCC. Methods: This is a pragmatic open-label, randomized controlled phase III, multicenter trial with non-inferiority design with regard to the primary endpoint overall survival and a superiority hypothesis for the experimental intervention dCRT with regard to the main secondary endpoint global HRQOL one year after randomization. The control intervention is nCRT followed by preplanned surgery and the experimental intervention is dCRT followed by surveillance and salvage esophagectomy only when needed to secure local tumor control. A target sample size of 1200 randomized patients is planned in order to reach 462 events (deaths) during follow-up. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT04460352.

Quality of Life in the First Year of Follow-Up in a Randomized Multicenter Trial Assessing the Role of Imaging after Radical Surgery of Stage IIB-C and III Cutaneous Melanoma (TRIM Study).

The benefit of imaging in the follow-up setting for high-risk melanoma patients is uncertain, and even less is known about the impact of intensive follow-up on the patient´s quality of life. In 2017, a Swedish prospective randomized multicenter study started, in which high-risk melanoma patients are randomly assigned 1:1 to follow-up by physical examinations +/- whole-body imaging. The first-year examinations are scheduled at 0, 6 and 12 months. The aim of this study was to investigate whether the patients´ health-related quality of life (HRQoL) and levels of anxiety and depression were affected at 1 year by imaging. Anxiety/depression and HRQoL were assessed at 0 and 12 months by the questionnaires Hospital Anxiety and Depression (HAD) scale and EORTC QLQ-C30 version 3. Expected baseline QLQ-C30 values for the patients were calculated using data from the general population. In total, 204 patients were analyzed. Mean differences in subscale scores at 1 year were not statistically significant either for HRQoL or for anxiety/depression. Baseline HRQoL did not differ from expected values in the general Swedish population. In conclusion, the patients in general coped well with the situation, and adding whole-body imaging to physical examinations did not affect the melanoma patients' HRQoL or levels of anxiety or depression.

Mandibular resection in patients with head and neck cancer: acute and long-term complications after reconstruction.

BACKGROUND: The treatment of head and neck cancer is an intensive multimodal treatment that has a great impact on the individual patient. AIMS/OBJECTIVES: This study aimed to evaluate acute and long-term complications associated with mandibular resections and reconstructions. MATERIAL AND METHODS: We retrospectively retrieved data on complications and recurrences among patients that underwent mandibular resections and reconstructions for treating oral cavity cancer (n = 190 patients) and osteoradionecrosis (ORN, n = 72). Reconstructions included composite grafts (n = 177), soft tissue flaps (n = 61), or primary closure without any graft (n = 24). RESULTS: Forty-two patients that underwent reconstructions with composite grafts displayed serious complications (Clavien-Dindo ≥ IIIa). The complication rates were similar between patients treated for oral cavity cancer and patients treated for ORN. Patients that underwent a primary closure without any graft, had a significantly lower risk of complications compared to patients that underwent the other treatments. After hospitalization, 181 patients (69%) had at least one complication. CONCLUSIONS: A majority of patients undergoing resection and reconstruction due to oral cancer/ORN suffered from postoperative complications regardless of indication, comorbidity status or reconstruction technique. The risk of Clavien-Dindo grade IIIa-V events was significantly lower for patients treated with primary closure without grafts. SIGNIFICANCE: The results from this study clarifies the importance of in-depth analyse prior to decision of treatment for patients with head and neck cancer.

Covid-19 in patients with chronic lymphocytic leukemia: clinical outcome and B- and T-cell immunity during 13 months in consecutive patients.

We studied clinical and immunological outcome of Covid-19 in consecutive CLL patients from a well-defined area during month 1-13 of the pandemic. Sixty patients (median age 71 y, range 43-97) were identified. Median CIRS was eight (4-20). Patients had indolent CLL (n = 38), had completed (n = 12) or ongoing therapy (n = 10). Forty-six patients (77%) were hospitalized due to severe Covid-19 and 11 were admitted to ICU. Severe Covid-19 was equally distributed across subgroups irrespective of age, gender, BMI, CLL status except CIRS (p < 0.05). Fourteen patients (23%) died; age ≥75 y was the only significant risk factor (p < 0.05, multivariate analysis with limited power). Comparing month 1-6 vs 7-13 of the pandemic, deaths were numerically reduced from 32% to 18%, ICU admission from 37% to 15% whereas hospitalizations remained frequent (86% vs 71%). Seroconversion occurred in 33/40 patients (82%) and anti-SARS-CoV-2 antibodies were detectable at six and 12 months in 17/22 and 8/11 patients, respectively. Most (13/17) had neutralizing antibodies and 19/28 had antibodies in saliva. SARS-CoV-2-specific T-cells (ELISpot) were detected in 14/17 patients. Covid-19 continued to result in high admission even among consecutive and young early- stage CLL patients. A robust and durable B and/or T cell immunity was observed in most convalescents.

A biomarker panel predicts recurrence-free survival in ulcerated primary cutaneous melanoma.

BACKGROUND: Ulceration is an independent adverse prognostic factor in cutaneous malignant melanoma (CMM). There is, however, a need for additional prognostic markers to identify patients with ulcerated stage I-II CMM who have a high-risk for recurrence. The aim of this study was to examine the prognostic impact of BRAF mutation, proliferation and presence of tumour infiltrating lymphocytes (TILs) in primary ulcerated CMM. MATERIAL AND METHODS: We have used a consecutive cohort consisting of 71 primary ulcerated CMM (T1b-T4b). BRAF mutation was detected using Cobas test and pyrosequencing. Protein expression of the proliferation marker Ki67 was analysed using immunohistochemistry. Presence of TILs was evaluated in representative hematoxylin-eosin stained formalin-fixed paraffin-embedded tumour sections. RESULTS: Proportion of BRAF mutated alleles, proliferation and presence of TILs all had a statistically significant impact on recurrence free survival in univariate analyses (HR 2.44, 95% CI 1.23-4.84, p = 0.011; HR 2.66, 95% CI 1.32-5.35, p = 0.006 respectively HR 0.48, 95% CI 0.24-0.98, p = 0.045). A trend test found a statistically significant decrease in the proportion of recurrence by including the three favourable factors (BRAF wildtype/low proportion of BRAF mutated alleles, low proliferation and high presence of TILs) (p = 0.0004). When at least two out of three factors were present there was a statistically significant association with longer recurrence free survival in the multivariate analysis (HR 0.30, 95% CI 0.15-0.61, p = 0.001) when adjusted for Breslow thickness, an established independent prognostic marker for CMM. CONCLUSION: Thus, this panel of markers could be an interesting novel concept for predicting the clinical outcome in patients with high-risk stage I-II ulcerated CMM.

Effect of Immediate Implant-Based Breast Reconstruction After Mastectomy With and Without Acellular Dermal Matrix Among Women With Breast Cancer: A Randomized Clinical Trial.

Importance: The use of acellular dermal matrix (ADM) in implant-based breast reconstructions (IBBRs) is established practice. Existing evidence validating ADMs proposed advantages, including improved cosmetics and more single-stage IBBRs, is lacking. Objective: To evaluate whether IBBR with ADM results in fewer reoperations and increased health-related quality of life (HRQoL) compared with conventional IBBR without ADM. Design, Setting, and Participants: This was an open-label, multicenter, randomized clinical trial of women with primary breast cancer who planned for mastectomy and immediate IBBR, with a 2-year follow-up for all participants. Participants were enrolled at 5 breast cancer units in Sweden and the United Kingdom between 2014 and May 2017. Exclusion criteria included previous radiotherapy and neo-adjuvant chemotherapy. Data were analyzed until August 2017. Interventions: Participants were allocated to immediate IBBR with or without ADM. Main Outcomes and Measures: The primary trial end point was number of reoperations at 2 years. HRQoL, a secondary end point, was measured as patient-reported outcome measures using 3 instruments from the European Organization for Research and Treatment of Cancer Quality of life Questionnaire. Results: From start of enrollment on April 24, 2014, to close of trial on May 10, 2017, a total of 135 women were enrolled (mean [SD] age, 50.4 [9.5] years); 64 were assigned to have an IBBR procedure with ADM and 65 to the control group who had IBBR without ADM. There was no statistically significant difference between groups for the primary outcome. Of 129 patients analyzed at 2-year follow-up, 44 of 64 (69%) had at least 1 surgical event in the ADM group vs 43 of 65 (66%) in the control group. In the ADM group, 31 patients (48%) had at least 1 reoperation on the ipsilateral side vs 35 (54%) in the control group. The overall number of reoperations on the ipsilateral side were 42 and 43 respectively. Within the follow-up time of 24 months, 9 patients (14%) in the ADM group had the implant removed compared with 7 (11%) in the control group. We found no significant mean differences in postoperative patient-reported HRQoL domains, including perception of body image (mean difference, 3; 99% CI, -11 to 17; P = .57) and satisfaction with cosmetic outcome (mean difference, 8; 99% CI, -6 to 20; P = .11). Conclusions and Relevance: Immediate IBBR with ADM did not yield fewer reoperations compared with conventional IBBR without ADM, nor was IBBR with ADM superior in terms of HRQoL or patient-reported cosmetic outcomes. Patients treated for breast cancer contemplating ADM-supported IBBR should be informed about the lack of evidence validating ADM's suggested benefits. Trial Registration: ClinicalTrials.gov Identifier: NCT02061527.