Objective To evaluate risk factors for the development of dysphagia after anterior cervical surgery. Methods The records of 249 patients who underwent anterior cervical surgery were reviewed. The ...presence and severity of dysphagia were assessed with the Dysphagia Disability Index 6 weeks and 3, 6, and 12 months after surgery. Age; sex; ethnicity; cigarette smoking; previous cervical surgeries; reoperation for same pathology; type of procedure, incision, and instrumentation; number and levels involved; side of procedure, length of surgery; and use of postoperative bracing were analyzed. Results During the first 6 months after surgery, 27 (10.8%) patients developed dysphagia. From these patients the presence of dysphagia at 6 weeks and at 3 and 6 months was 88.8%, 29.6%, and 7.4%, respectively. By 12 months, dysphagia had resolved in all cases. The mean age of patients with dysphagia was 55 years (SD 12.98) and 50 years (SD 12.07) in patients without dysphagia ( P = 0.05). Dysphagic patients had an average of 2.2 (SD 1.15) levels operated compared with 1.84 (SD 0.950) in nondysphagic patients ( P = 0.05). Patients who developed dysphagia were most often treated at C4-5 (67%) and C5-6 (81%: P < 0.001). Although mean operative time was slightly longer in patients with dysphagia (186 minutes) compared with those without (169 minutes), the difference was not significant. Conclusions In our patients, the incidence of dysphagia was low, and it had completely resolved at 12 months in all cases. Risk factors for dysphagia were multilevel procedures, involvement of C4-5 and C5-6, and age.
Several current immunotherapy approaches target private neoantigens derived from mutations that are unique to individual patients' tumors. However, immunotherapeutic agents can also be developed ...against public neoantigens derived from recurrent mutations in cancer driver genes. The latter approaches target proteins that are indispensable for tumor growth, and each therapeutic agent can be applied to numerous patients. Here we review the opportunities and challenges involved in the identification of suitable public neoantigen targets and the development of therapeutic agents targeting them.
Primary sarcomas of the kidney in adults are rare. In the handful of published reports of all soft tissue sarcomas, DNA ploidy has correlated with histologic grade and outcome. This report presents ...the clinicopathologic and flow cytometric features of 17 cases of primary renal sarcoma (seven men and ten women, ages 28–69 years). Presenting symptoms included abdominal and back pain and hematuria. Stages at diagnosis were I, in three patients; II, five patients; III, two patients; and IV, two patients. Eight tumors were leiomyosarcoma, two malignant fibrous histiocytoma, one hemangiopericytoma, one fibrosarcoma, and five unclassified. Tumors measured 5.5 to 23 cm, seven contained marked nuclear pleomorphism, seven were extensively necrotic, and mitotic rate was 1 to 33 per 10 high‐power fields. Seven tumors showed aneuploidy and five were diploid. Thirteen patients were dead of disease after a mean of 23 months and two were alive with known metastases at 29 and 33 months, respectively. Ploidy pattern and outcome or time to death were not correlated, but aneuploidy correlated with histologic grade, marked nuclear pleomorphism (P < 0.05), extensive necrosis (p < 0.01), and high mitotic rate (0.05 < P < 0.10). The authors conclude that although DNA ploidy does correlate with histologic grade, for primary renal sarcomas, whose prognosis in this series was extremely poor, it does not correlate with outcome.
To evaluate the outcome and toxicity of a sphincter-sparing treatment strategy in the management of patients with anal-rectal melanoma.
Between 1989 and 2000, 23 patients with invasive anal-rectal ...melanoma were managed with sphincter-sparing surgical resection and adjuvant radiation. Surgery consisted of primary local excision, as well as dissection for patients with documented regional nodal disease. Adjuvant radiation was delivered using a hypofractionated regimen of 30 Gy in five fractions over 2.5 weeks. Adjuvant systemic therapy was delivered to nine patients: cytotoxic chemotherapy in seven and immunotherapy in two.
After a median follow-up of 32 months, 15 patients had relapsed and 15 patients had died. The actuarial 5-year overall, disease-specific, disease-free, and distant metastasis-free survival rates were 31%, 36%, 37%, and 35%, respectively. The actuarial 5-year local and regional nodal control rates were 74% and 84%, respectively. No patient had locoregional failure as the sole site of failure and no patient required salvage abdominoperineal resection (APR). By univariate analysis, patients with nodal disease at presentation had a decreased actuarial 5-year disease-specific (0% v 45%, P =.004), disease-free (0% v 45%, P <.001), and distant metastasis-free survival (0% v 42%, P <.001). The actuarial complication-free survival rate was 71%. Two patients developed mild scrotal edema (grade 1), and four patients developed moderate proctitis requiring prolonged medical management (grade 2).
Sphincter-sparing local excision and adjuvant radiation is well tolerated and can effectively control local-regional disease while avoiding the functional morbidity of APR.
This phase I clinical trial was conducted to determine the safety, efficacy, and molecular effects of sorafenib with temsirolimus in patients with advanced melanoma.
Patients with stage IV or ...unresectable or recurrent stage III melanoma and Eastern Cooperative Oncology Group performance status of 0 to 1 were eligible. Sorafenib was given orally once or twice daily and temsirolimus was given i.v. weekly, both starting on day 1, with a 4-week cycle. Responses were assessed every 2 cycles per Response Evaluation Criteria in Solid Tumors criteria. Consenting patients with accessible tumors underwent optional tumor biopsies before treatment and after the second infusion of temsirolimus. Tumor biopsies were analyzed for activating mutations in BRAF and NRAS, and for expression of P-extracellular signal-regulated kinase (P-ERK) and P-S6 proteins.
A total of 25 patients were accrued to the study. The maximum tolerated doses were sorafenib 400 mg every morning and 200 mg every evening and temsirolimus 25 mg i.v. weekly. Dose-limiting toxicities included thrombocytopenia, hand-foot syndrome, serum transaminase elevation, and hypertriglyceridemia. There were no complete or partial responses with the combination; 10 patients achieved stabilization of disease as their best response. The median progression-free survival was 2.1 months. Matching pretreatment and day 15 tumor biopsies showed marked inhibition of P-S6 with treatment in 3 of 4 evaluable patients, but minimal inhibition of P-ERK.
Combination therapy with sorafenib and temsirolimus resulted in significant toxicity at higher dose levels, failed to achieve any clinical responses in genetically unselected patient population, and did not inhibit P-ERK.
Fifty-two study participants underwent cervical spine surgery using intraoperative Iso-C imaging with or without spinal navigation.
To evaluate prospectively the feasibility, advantages, limitations, ...and applications of Iso-C in cervical spine surgery.
Existing stereotactic spinal navigational systems images must be acquired before surgery and typically require cumbersome point-to-point registration. Intraoperative computed tomography (CT) and magnetic resonance imaging (MRI) provide real-time information but can restrict access to the patient, preclude the use of traditional operating room tables, and are time-consuming. The Iso-C allows quick, CT-quality, real-time data acquisition without restricting access to the patient. The data acquired can be automatically transferred to navigational systems with the immediate ability to navigate for anterior or posterior cervical spine procedures.
High-resolution isotropic three-dimensional data sets were acquired using the Iso-C intraoperative fluoroscopy in 52 cervical spine cases. In 30 cases, the data were imported automatically to the StealthStation Treon to support neuronavigation. In 22 cases, a postprocedural intraoperative CT was obtained with the Iso-C primarily to assess the extent of osseous decompression and/or the accuracy of implants or instrumentation. In most cases, a postoperative high-resolution CT image was obtained and compared with the Iso-C data.
Successful automated registration suitable for navigation was attained for all anterior and posterior cervical spinal cases. The postprocedural intraoperative Iso-C data were 100% concordant with those of postoperative high-resolution CT as determined by a blinded neuroradiologist.
Iso-C intraoperative fluoroscopy is an accurate and rapid way to perform CT-quality image-guided navigation in cervical spinal surgery. In most cases, it obviates the need for postoperative imaging.
Intermittent androgen deprivation therapy (ADT) in biochemically recurrent castration-naïve prostate cancer is non-inferior to continuous therapy. We hypothesised that finite-duration abiraterone ...acetate plus prednisone (Abi +P) added to ADT will further reduce the duration of treatment exposure by prolonging time to prostate-specific antigen (PSA) recurrence without impacting eugonad state recovery.
This phase II, randomised, open-label trial enrolled patients with rising PSA ≥ 0.2 ng/ml after radical prostatectomy and/or a PSA ≥ 1 following radiotherapy. Patients were randomised 1:1 to receive Abi (1 g PO daily) + P (5 mg PO daily) + ADT or ADT alone for 8 months. The primary end-point was PSA-free survival difference at 1 year following completion of therapy.
Between February 2013 and July 2016, 200 patients were enrolled. Of 100 patients randomised to each arm, 99 in the Abi +P arm and 98 in the ADT arm were evaluable. Median follow-up was 64.4 months. Median PSA-free survival was 27.0 months for the Abi +P-treated group versus 19.9 months for the ADT-treated group (hazard ratio HR 0.64, 95% confidence interval CI 0.47–0.87). The PSA-free survival at 1 year post-treatment completion was 98% for the Abi +P group and 88% for the ADT group. Median time to eugonad state was 13.1 months for the abiraterone-treated group and 12.8 months for the ADT-treated group. Median eugonad PSA-free survival was 12.5 months for the abiraterone-treated group versus 9.0 for the ADT-treated group (HR 0.72, 95% CI 0.53–0.98). There were no significant between-group differences in androgen deprivation-related adverse events.
In men with biochemically recurrent prostate cancer following definitive treatment of the primary, finite duration treatment with ADT and Abi +P results in a significantly longer PSA relapse-free interval than treatment with ADT alone.
•This trial investigated abiraterone in biochemically recurrent prostate cancer.•All patients had castration-naïve disease.•Abiraterone was added to ADT for 8 months.•This led to a significantly increased PSA-free survival compared to ADT alone.•The interval to subsequent systemic prostate cancer treatment was thus prolonged.
Several predictive biomarkers are currently approved or are under investigation for the selection of patients for checkpoint blockade. Tumor PD-L1 expression is used for stratification of non-small ...cell lung (NSCLC) patients, with tumor mutational burden (TMB) also being explored with promising results, and mismatch-repair deficiency is approved for tumor site-agnostic disease. While tumors with high PD-L1 expression, high TMB, or mismatch repair deficiency respond well to checkpoint blockade, tumors with lower PD-L1 expression, lower mutational burdens, or mismatch repair proficiency respond much less frequently.
We studied two patients with unexpected responses to checkpoint blockade monotherapy: a patient with PD-L1-negative and low mutational burden NSCLC and one with mismatch repair proficient colorectal cancer (CRC), both of whom lack the biomarkers associated with response to checkpoint blockade, yet achieved durable clinical benefit. Both maintained T-cell responses in peripheral blood to oncogenic driver mutations - BRAF-N581I in the NSCLC and AKT1-E17K in the CRC - years after treatment initiation. Mutation-specific T cells were also found in the primary tumor and underwent dynamic perturbations in the periphery upon treatment.
These findings suggest that T cell responses to oncogenic driver mutations may be more prevalent than previously appreciated and could be harnessed in immunotherapeutic treatment, particularly for patients who lack the traditional biomarkers associated with response. Comprehensive studies are warranted to further delineate additional predictive biomarkers and populations of patients who may benefit from checkpoint blockade.
Previous studies investigating the impact of comorbidities on the effectiveness of biologic agents have been relatively small and of short duration and have not compared classes of biologic agents.
...To determine the association between type 2-related comorbidities and biologic agent effectiveness in adults with severe asthma (SA).
This cohort study used International Severe Asthma Registry data from 21 countries (2017-2022) to quantify changes in four outcomes before and after biologic therapy-annual asthma exacerbation rate, FEV
% predicted, asthma control, and long-term oral corticosteroid daily dose-in patients with or without allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyps (NPs), NPs, or eczema/atopic dermatitis.
Of 1,765 patients, 1,257, 421, and 87 initiated anti-IL-5/5 receptor, anti-IgE, and anti-IL-4/13 therapies, respectively. In general, pre- versus post-biologic therapy improvements were noted in all four asthma outcomes assessed, irrespective of comorbidity status. However, patients with comorbid CRS with or without NPs experienced 23% fewer exacerbations per year (95% CI, 10-35%;
< 0.001) and had 59% higher odds of better post-biologic therapy asthma control (95% CI, 26-102%;
< 0.001) than those without CRS with or without NPs. Similar estimates were noted for those with comorbid NPs: 22% fewer exacerbations and 56% higher odds of better post-biologic therapy control. Patients with SA and CRS with or without NPs had an additional FEV
% predicted improvement of 3.2% (95% CI, 1.0-5.3;
= 0.004), a trend that was also noted in those with comorbid NPs. The presence of allergic rhinitis or atopic dermatitis was not associated with post-biologic therapy effect for any outcome assessed.
These findings highlight the importance of systematic comorbidity evaluation. The presence of CRS with or without NPs or NPs alone may be considered a predictor of the effectiveness of biologic agents in patients with SA.
Dengue viruses (DENV1-4) are mosquito-borne flaviviruses estimated to cause up to ∼400 million infections and ∼100 million dengue cases each year. Factors that contribute to protection from and risk ...of dengue and severe dengue disease have been studied extensively but are still not fully understood. Results from Phase 3 vaccine efficacy trials have recently become available for one vaccine candidate, now licensed for use in several countries, and more Phase 2 and 3 studies of additional vaccine candidates are ongoing, making these issues all the more urgent and timely. At the “Summit on Dengue Immune Correlates of Protection”, held in Annecy, France, on March 8–9, 2016, dengue experts from diverse fields came together to discuss the current understanding of the immune response to and protection from DENV infection and disease, identify key unanswered questions, discuss data on immune correlates and plans for comparison of results across assays/consortia, and propose a research agenda for investigation of dengue immune correlates, all in the context of both natural infection studies and vaccine trials.
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