Long-term safety of OnabotulinumtoxinA treatment in chronic migraine patients: a five-year retrospective study.

Background: Real-world studies have shown the sustained therapeutic effect and favourable safety profile of OnabotulinumtoxinA (BoNTA) in the long term and up to 4 years of treatment in chronic migraine (CM). This study aims to assess the safety profile and efficacy of BoNTA in CM after 5 years of treatment in a real-life setting. Methods: We performed a retrospective chart review of patients with CM in relation to BoNTA treatment for more than 5 years in 19 Spanish headache clinics. We excluded patients who discontinued treatment due to lack of efficacy or poor tolerability. Results: 489 patients were included [mean age 49, 82.8% women]. The mean age of onset of migraine was 21.8 years; patients had CM with a mean of 6.4 years (20.8% fulfilled the aura criteria). At baseline, patients reported a mean of 24.7 monthly headache days (MHDs) and 15.7 monthly migraine days (MMDs). In relation to effectiveness, the responder rate was 59.1% and the mean reduction in MMDs was 9.4 days (15.7 to 6.3 days; p < 0.001). The MHDs were also reduced by 14.9 days (24.7 to 9.8 days; p < 0.001). Regarding the side effects, 17.5% experienced neck pain, 17.3% headache, 8.5% eyelid ptosis, 7.5% temporal muscle atrophy and 3.2% trapezius muscle atrophy. Furthermore, after longer-term exposure exceeding 5 years, there were no serious adverse events (AE) or treatment discontinuation because of safety or tolerability issues. Conclusion: Treatment with BoNTA led to sustained reductions in migraine frequency, even after long-term exposure exceeding 5 years, with no evidence of new safety concerns.

Sentinel lymph node biopsy before and after neoadjuvant chemotherapy in cN0 breast cancer patients: impact on axillary morbidity and survival-a propensity score cohort study.

PURPOSE: In patients with clinically lymph node-negative (cN0) breast cancer, performing sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NACT) has been preferentially embraced in comparison to before NACT. However, survival outcomes associated with both strategies remain understudied. We aimed to compare the axillary lymphadenectomy (ALND) rate, disease-free survival (DFS), and overall survival (OS), between two strategies. METHODS: We included 310 patients in a retrospective observational study. SNLB was performed before NACT from December 2006 to April 2014 (107 cases) and after NACT from May 2014 to May 2020 (203 patients). An inverse probability of treatment weighting (IPTW) method was applied to homogenize both groups. Hazard ratios (HR) and odd ratios (OR) are reported with 95% confidence intervals (95%CI). RESULTS: The lymphadenectomy rate was 29.9% before NACT and 7.4% after NACT (p < 0.001), with an OR of 5.35 95%CI (2.7-10.4); p = .002. After 4 years of follow-up, SLNB after NACT was associated with lower risk for DFS, HR 0.42 95%CI (0.17-1.06); p = 0.066 and better OS, HR 0.21 CI 95% (0.07-0.67); p = 0.009 than SLNB before NACT. After multivariate analysis, independent adverse prognostic factors for OS included SLNB before NACT, HR 3.095 95%CI (2.323-4.123), clinical nonresponse to NACT, HR 1.702 95% CI (1.012-2.861), and small tumors (cT1) with high proliferation index, HR 1.889 95% (1.195-2.985). CONCLUSION: Performing SLNB before NACT results in more ALND and has no benefit for patient survival. These findings support discontinuing the practice of SLNB before NACT in patients with cN0 breast cancer.

Observational Retrospective Study in Patients Treated with Galcanezumab as Preventive Treatment for Migraine: The ORYGAM Study.

INTRODUCTION: The efficacy of galcanezumab has been demonstrated in randomized controlled trials, but evidence about its use under clinical practice conditions is still limited. This study aimed to describe the characteristics of the patients treated with galcanezumab in routine clinical practice in Spain as well as treatment patterns, persistence, and effectiveness. METHODS: A retrospective chart review study was carried out in six hospitals. Information of adults with migraine, who started treatment with galcanezumab between November 2019 and September 2021, was analyzed until end or loss of follow-up. Continuous variables were described as mean (standard deviation, SD) and median (interquartile range, IQR), and categorical variables as frequency and percentages. Persistence to treatment was estimated using Kaplan-Meier analysis. RESULTS: A total of 314 patients were analyzed over median follow-up period of 17.5 months (13.8-20.7), with a mean age of 46.3 (12.6), 85% women, 80.6% chronic migraine, and reporting a mean of monthly migraine days of 16.7 (7.8). Overall, 72.9% had comorbid conditions, with anxiety and depression disorders being the most frequent. More than 60% had received ≥ 6 previous preventive drugs, the most common being antiepileptics, antidepressants, and botulinum toxin (95.2%, 89.8% and 84.1%, respectively). Overall, 60.3% of the patients with other preventive treatments maintained them after galcanezumab initiation. The median time on galcanezumab was 14.6 months (9.4-22.8); 95.7%, 82.0%, 76.2% and 59.8% of patients were persistent to treatment at 3, 6, 9 and 12 months, respectively. Of the patients who discontinued (151: 48.1%), 57.6% were due to lack of effectiveness and 31.1% were due to improvement in migraine. The average reduction of monthly migraine days at 3, 6, 9 and 12 months was 7.9 (7.2), 9.1 (7.5), 8.8 (6.6) and 9.0 (6.9) days, respectively. CONCLUSIONS: In real clinical practice, galcanezumab is an effective treatment and has a high persistence in patients with migraine, mostly chronic and with multiple use of previous preventive treatments.

Hype or hope? A review of challenges in balancing tumor control and treatment toxicity in breast cancer from the perspective of the radiation oncologist

The aim of this article is to discuss the challenges and new strategies in managing breast cancer patients, with a specific focus on radiation oncology and the importance of balancing oncologic outcomes with quality of life and post-treatment morbidity. A comprehensive literature review was conducted to identify advances in the management of breast cancer, exploring de-escalation strategies, hypofractionation schemes, predictors and tools for reducing toxicity (radiation-induced lymphocyte apoptosis, deep inspiration breath-hold, adaptive radiotherapy), enhancer treatments (hyperthermia, immunotherapy) and innovative diagnostic modalities (PET-MRI, omics). Balancing oncologic outcomes with quality of life and post-treatment morbidity is crucial in the era of personalized medicine. Radiotherapy plays a critical role in the management of breast cancer patients. Large randomized trials are necessary to generalize some practices and cost remains the main obstacle for many innovations that are already applicable (AU)

Hype or hope? A review of challenges in balancing tumor control and treatment toxicity in breast cancer from the perspective of the radiation oncologist.

The aim of this article is to discuss the challenges and new strategies in managing breast cancer patients, with a specific focus on radiation oncology and the importance of balancing oncologic outcomes with quality of life and post-treatment morbidity. A comprehensive literature review was conducted to identify advances in the management of breast cancer, exploring de-escalation strategies, hypofractionation schemes, predictors and tools for reducing toxicity (radiation-induced lymphocyte apoptosis, deep inspiration breath-hold, adaptive radiotherapy), enhancer treatments (hyperthermia, immunotherapy) and innovative diagnostic modalities (PET-MRI, omics). Balancing oncologic outcomes with quality of life and post-treatment morbidity is crucial in the era of personalized medicine. Radiotherapy plays a critical role in the management of breast cancer patients. Large randomized trials are necessary to generalize some practices and cost remains the main obstacle for many innovations that are already applicable.

Determining the optimal interval between neoadjuvant radiochemotherapy and surgery in rectal cancer: a retrospective cohort study.

INTRODUCTION: In locally advanced rectal cancer, the optimal interval between completion of neoadjuvant radiochemotherapy (RT-ChT) and surgical resection remains unclear due to contradictory data on the benefits of extending this interval. Therefore, the aim of this retrospective study was to determine the impact of this interval on outcomes in patients treated for rectal cancer at our center. METHODS: We retrospectively reviewed 382 consecutive patients treated for stage II/III rectal cancer between October 1, 2012, and December 31, 2017. We evaluated four different cut-off points (56, 63, 70, and 77 days) to determine which had the greatest impact on treatment outcomes. RESULTS: The median time between completion of RT-ChT and surgery was 67.2 days (range, 28-294). Intervals > 8 weeks (56 days) were associated with worse therapeutic outcomes. Specifically, an interval ≥ 77 days was associated with a significant decrease in overall survival (OS; 84% vs. 70%; p = 0.004), which is why we selected this interval for the comparative analysis. Several outcome variables were significantly better in the short interval (< 77 days) group, including margin involvement (5.2% vs. 13.9%; p = 0.01), sphincter preservation (78% vs. 59.3%; p = 0.003), and distant dissemination (22.6% vs. 32.5%; p = 0.04). No significant between-group differences were found in complete/nearly complete response rates (19.2% vs. 24.4%; p = 0.3). Time to surgery was statistically significant on both the univariate and multivariate analyses. CONCLUSIONS: Our findings suggest that surgery should not be delayed more than 8 weeks (56 days) after neoadjuvant treatment. An interval > 8 weeks should only be considered in patients who demonstrate a good response to neoadjuvant RT-ChT.

Outcomes and computed tomography radiomic features extraction in soft tissue sarcomas treated with neoadjuvant radiation therapy.

BACKGROUND: The aim of the study was to evaluate the management, toxicity and treatment responses of patients treated with neoadjuvant radiotherapy (NART) for soft tissue sarcomas (STS) and to analyse the potential of radiomic features extracted from computed tomography (CT) scans. MATERIALS AND METHODS: This is a retrospective and exploratory study with patients treated between 2006 and 2019. Acute and chronic toxicities are evaluated. Local progression free survival (LPFS), distant progression free survival (DPFS) and overall survival (OS) are analysed. Radiomic features are obtained. RESULTS: A total of 25 patients were included. Median follow-up is 24 months. Complications in surgical wound healing were observed in 20% of patients, chronic fibrosis was documented as grade 1 (12%) and grade 2 (12%) without grade 3 events and chronic lymphedema as grade 1 (8%) and grade 2 (20%) without grade 3 events. Survival variables were LPFS 76%, DPFS 62% and OS 67.2% at 2-year follow-up. CT radiomics features were associated significantly with local control (GLCM-correlation), systemic control (HUmin, HUpeak, volume, GLCM-correlation and GLZLM-GLNU) and OS (GLZLM-SZE). CONCLUSIONS: STS treated with NART in our centre associate with an OS and toxicity comparable to other series. CT radiomic features have a prognosis potential in STS risk stratification. The results of our study may serve as a motivation for future prospective studies with a greater number of patients.

MAB-MIG: registry of the spanish neurological society of erenumab for migraine prevention.

BACKGROUND: Erenumab was approved in Europe for migraine prevention in patients with ≥ 4 monthly migraine days (MMDs). In Spain, Novartis started a personalized managed access program, which allowed free access to erenumab before official reimbursement. The Spanish Neurological Society started a prospective registry to evaluate real-world effectiveness and tolerability, and all Spanish headache experts were invited to participate. We present their first results. METHODS: Patients fulfilled the ICHD-3 criteria for migraine and had ≥ 4 MMDs. Sociodemographic and clinical data were registered as well as MMDs, monthly headache days, MHDs, prior and concomitant preventive treatment, medication overuse headache (MOH), migraine evolution, adverse events, and patient-reported outcomes (PROs): headache impact test (HIT-6), migraine disability assessment questionnaire (MIDAS), and patient global improvement change (PGIC). A > 50% reduction of MMDs after 12 weeks was considered as a response. RESULTS: We included 210 patients (female 86.7%, mean age 46.4 years old) from 22 Spanish hospitals from February 2019 to June 2020. Most patients (89.5%) suffered from chronic migraine with a mean evolution of 8.6 years. MOH was present in 70% of patients, and 17.1% had migraine with aura. Patients had failed a mean of 7.8 preventive treatments at baseline (botulinum toxin type A-BoNT/A-had been used by 95.2% of patients). Most patients (67.6%) started with erenumab 70 mg. Sixty-one percent of patients were also simultaneously taking oral preventive drugs and 27.6% were getting simultaneous BoNT/A. Responder rate was 37.1% and the mean reduction of MMDs and MHDs was -6.28 and -8.6, respectively. Changes in PROs were: MIDAS: -35 points, HIT-6: -11.6 points, PIGC: 4.7 points. Predictors of good response were prior HIT-6 score < 80 points (p = 0.01), ≤ 5 prior preventive treatment failures (p = 0.026), absence of MOH (p = 0.039), and simultaneous BoNT/A treatment (p < 0.001). Twenty percent of patients had an adverse event, but only two of them were severe (0.9%), which led to treatment discontinuation. Mild constipation was the most frequent adverse event (8.1%). CONCLUSIONS: In real-life, in a personalized managed access program, erenumab shows a good effectiveness profile and an excellent tolerability in migraine prevention in our cohort of refractory patients.

Short-Course Radiotherapy in Locally Advanced Rectal Cancer.

INTRODUCTION: To date, we do not know the best therapeutic scheme in locally advanced rectal cancer when patients are older or have comorbidities. METHODS: In 2009, we established a prospective treatment protocol that included short-course preoperative radiotherapy (RT) with standard surgery +/- chemotherapy in frail patients, mostly older than 80 years or with comorbidities. RESULTS: We included 87 patients; the mean follow-up was 43.5 months (0.66-106.3). Disease-specific survival and disease-free survival at 36 months were 86.3% and 82.8%; at 60 months, they were 78.2% and 78%, respectively, with a local recurrence rate of 2.5%. The rate of late radiotoxicity was 9% in the form of sacral insufficiency fracture and small bowel obstruction with one death. The interval before surgery varied according to the involvement of the mesorectal fascia, but it was less than 2 weeks in 45% of cases. The rate of R0 was 95%. Surgical complications included abdominal wound dehiscence (3.5%), anastomotic leak (2.4%), and reoperations (11.5%). Downstaging was observed in 51% of the cases, regardless of the interval before surgery. DISCUSSION: Therapeutic outcomes in our group of elderly patients and/or patients with comorbidities with neoadjuvant short-course RT are such as those of the general population treated with neoadjuvant RT-chemotherapy, all with acceptable toxicity. Therefore, this treatment scheme, with short-course preoperative RT, would be the most appropriate in this group of patients.