[Clinical efficacy of induction chemoimmunotherapy for locally advanced hypopharyngeal carcinoma: a prospective phase â ¡ study].

Objective: To evaluate the objective response rate (ORR) of induction chemoimmunotherapy with camrelizumab plus TPF (docetaxel, cisplatin, and capecitabine) for locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) and potential predictive factors for ORR. Methods: A single-center, prospective, phase 2 and single-arm trial was conducted for evaluating antitumor activity of camrelizumab+TPF(docetaxel+cisplatin+capecitabine) for LA HSCC between May 21, 2021 and April 15, 2023, patients admitted to the Eye & ENT Hospital affiliated with Fudan University. The primary endpoint was ORR, and enrolled patients with LA HSCC at T3-4N0-3M0 received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg day 1, docetaxel 75 mg/m2 day 1, cisplatin 25 mg/m2 days 1-3, and capecitabine 800 mg/m2 days 1-14. Patients were assigned to radioimmunotherapy when they had complete response or partial response (PR)>70% (Group A), or assigned to surgery plus adjuvant radiotherapy/chemoradiotherapy when they had PR≤70% (Group B), and the responses were defined by using tumor volume evaluation system. Tumor diameter was also used to assess the treatment responses by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Use SPSS 23.0 software was used to analyze the data. Results: A total of 51 patients were enrolled who underwent the induced chemoimmunotherapy for three cycles, and all were males, aged 35-69 years old. After three cycles of induction immunochemotherapy, 42 (82.4%) patients existed in Group A (complete response or PR>70%) and 9 patients (17.6%) in Group B (PR≤70%), the ORR was 82.4%. The primary endpoint achieved expected main research objectives. Compared to the patients of Group A, the patients of Group B showed the higher T stage and the larger volume of primary tumor before induced immunochemotherapy, and also had the less regression of tumor volume after induced immunochemotherapy (all P<0.05). The optimal cutoff value of pre-treatment tumor volume for predicting ORR was 39 cm3. The T stage (OR=12.71, 95%CI: 1.4-112.5, P=0.022) and the volume (OR=7.1, 95%CI: 1.4-36.8, P=0.018) of primary tumor were the two main factors affecting ORR rate of induction chemoimmunotherapy. Conclusion: The induction chemoimmunotherapy with camrelizumab plus TPF shows an encouraging antitumor efficacy in LA HSCC.

Induction Toripalimab and Chemotherapy for Organ Preservation in Locally Advanced Laryngeal and Hypopharyngeal Cancer: A Single-Arm Phase II Clinical Trial.

PURPOSE: The aim of this study was to assess the efficacy, toxicities, and potential role of larynx preservation of induction chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitor in locally advanced laryngeal and hypopharyngeal cancer. PATIENTS AND METHODS: This is a single-arm phase II study. Patients with histopathologically confirmed, resectable locally advanced laryngeal/hypopharyngeal squamous cell carcinoma and Eastern Cooperative Oncology Group Performance Status 0-1 were eligible. Three cycles of induction chemotherapy (paclitaxel 175 mg/m2 d1, cisplatin 25 mg/m2 d1-3) combined with PD-1 inhibitor (toripalimab 240 mg d0) were administered. Response assessment was performed after induction chemoimmunotherapy using RECIST 1.1 criteria. Patients with a complete/partial response of the primary tumor received concurrent chemoradiation, followed by maintenance therapy of toripalimab. Otherwise, patients were referred to surgery, followed by adjuvant (chemo) radiation and maintenance therapy of toripalimab. The primary endpoint is a larynx preservation rate at 3 months postradiation. RESULTS: Twenty-seven patients were enrolled. Most cases exhibited stage IV disease (81.5%), with T4 representing 37.0%. Five patients underwent pretreatment tracheostomy because of impaired larynx function. Overall response rate of induction chemoimmunotherapy was 85.2%. At 3 months postradiation, the larynx preservation rate was 88.9%. With a median follow-up of 18.7 months, the 1-year overall survival rate, progression-free survival rate, and larynx preservation rate were 84.7%, 77.6%, and 88.7%, respectively. When excluding those with pretreatment tracheostomy, the 1-year larynx preservation rate was 95.5%. Exploratory analysis revealed that relapse correlated with enrichment of RNA signature of hypoxia and M2 macrophage-associated genes. CONCLUSIONS: Induction toripalimab combined with chemotherapy provided encouraging activity, promising larynx preservation rate and acceptable toxicity in this cohort of extensively locally advanced laryngeal and hypopharyngeal cancer.

Nationwide Use and Outcome of Surgery for Locally Advanced Pancreatic Cancer Following Induction Chemotherapy.

BACKGROUND: Several international high-volume centers have reported good outcomes after resection of locally advanced pancreatic cancer (LAPC) following chemo(radio)therapy, but it is unclear how this translates to nationwide clinical practice and outcome. This study aims to assess the nationwide use and outcome of resection of LAPC following induction chemo(radio)therapy. PATIENTS AND METHODS: A multicenter retrospective study including all patients who underwent resection for LAPC following chemo(radio)therapy in all 16 Dutch pancreatic surgery centers (2014-2020), registered in the mandatory Dutch Pancreatic Cancer Audit. LAPC is defined as arterial involvement > 90° and/or portomesenteric venous > 270° involvement or occlusion. RESULTS: Overall, 142 patients underwent resection for LAPC, of whom 34.5% met the 2022 National Comprehensive Cancer Network criteria. FOLFIRINOX was the most commonly (93.7%) used chemotherapy [median 5 cycles (IQR 4-8)]. Venous and arterial resections were performed in 51.4% and 14.8% of patients. Most resections (73.9%) were performed in high-volume centers (i.e., ≥ 60 pancreatoduodenectomies/year). Overall median volume of LAPC resections/center was 4 (IQR 1-7). In-hospital/30-day major morbidity was 37.3% and 90-day mortality was 4.2%. Median OS from diagnosis was 26 months (95% CI 23-28) and 5-year OS 18%. Surgery in high-volume centers [HR = 0.542 (95% CI 0.318-0.923)], ypN1-2 [HR = 3.141 (95% CI 1.886-5.234)], and major morbidity [HR = 2.031 (95% CI 1.272-3.244)] were associated with OS. CONCLUSIONS: Resection of LAPC following chemo(radio)therapy is infrequently performed in the Netherlands, albeit with acceptable morbidity, mortality, and OS. Given these findings, a structured nationwide approach involving international centers of excellence would be needed to improve selection of patients with LAPC for surgical resection following induction therapy.

Clinical status of induction therapy incorporating a hypomethylating agent for newly diagnosed adult acute myeloid leukemia compared to the standard 7+3 regimen.

INTRODUCTION: Cytarabine and anthracycline combination therapy (7 + 3 regimen) is the standard care for induction chemotherapy in adult patients with acute myeloid leukemia (AML). Although this intensive regimen achieves a high response rate, it is highly toxic, especially in elderly or frail patients. Hypomethylating agents approved initially for high-risk myelodysplastic syndrome had longer survival times than conventional care in elderly patients with newly diagnosed AML. AREAS COVERED: We summarize the latest information regarding induction therapy using hypomethylating agents (azacitidine and decitabine) for newly diagnosed AML. EXPERT OPINION: For untreated patients ineligible for an intensive regimen, a phase III trial exhibited the survival benefit of adding the highly selective BCL2 inhibitor venetoclax to azacitidine. The National Comprehensive Cancer Network guidelines recommend azacitidine or decitabine plus venetoclax as an option for patients with poor-risk AML, including those with TP53 mutations and AML with the cytogenetic features of myelodysplastic syndrome. Future studies should evaluate positioning this combination as an induction therapy for younger patients eligible for hematopoietic stem cell transplantation. Without randomized trials, propensity score matching analysis suggested a comparable prognosis between azacitidine combination and intensive chemotherapy. Considering the feasibility of a doublet regimen incorporating azacitidine, a triplet regimen should be examined.

Induction Chemotherapy With 5-Fluorouracil, Cisplatin, and Cetuximab in Advanced Head and Neck Squamous Cell Carcinoma.

BACKGROUND/AIM: Chemoradiotherapy (CRT) with high-dose cisplatin has become the standard of care for larynx preservation in patients with locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). However, the long-term results are unsatisfactory. Induction chemotherapy (ICT) with docetaxel/cisplatin/5-fluorouracil (TPF) is associated with hematologic toxicity, and a safer therapy with comparable efficacy is desired. We conducted a pilot study to investigate the efficacy and safety of 5-fluorouracil/cisplatin/cetuximab (FPE) therapy as a candidate regimen for ICT in comparison with TPF. PATIENTS AND METHODS: Patients with stage cN2/3 LA-SCCHN of the larynx/oropharynx/hypopharynx were treated with FPE or TPF followed by radiotherapy. We reviewed patients' medical records and evaluated treatment efficacy and safety retrospectively. RESULTS: The response rates for ICT and ICT-radiotherapy were 71% and 93%, respectively, in the FPE group and 90% and 89%, respectively, in the TPF group. The 1-year progression-free and overall survival rates were 57% and 100%, respectively, in the FPE group and 70% and 90%, respectively, in the TPF group. TPF was linked to significantly higher rates of Grade 3/4 hematologic toxicity during ICT. The rates of Grade 3 or higher toxicity did not differ between the two groups during radiotherapy. CONCLUSION: The efficacy of ICT was comparable between the FPE and TPF groups, whereas FPE was associated with less toxicity. It is suggested that FPE therapy is an alternative ICT regimen to TPF therapy, but further long-term follow-up is needed.

Hepcidin and Iron Status in Patients With Inflammatory Bowel Disease Undergoing Induction Therapy With Vedolizumab or Infliximab.

BACKGROUND: Hepcidin, the systemic iron regulator, could be critical in differentiating iron deficiency (ID) from functional iron restriction in inflammatory bowel disease (IBD). We assessed hepcidin as a diagnostic ID marker and explored the relationship between hepcidin and its regulators in patients with IBD undergoing induction therapy with infliximab (IFX) or vedolizumab (VEDO). METHODS: Patients with active IBD receiving induction therapy with IFX or VEDO were included. Serum samples at baseline and after 6 weeks of induction therapy were analyzed for hepcidin, inflammation- and hypoxia-associated cytokines, and oxidative stress. Data were analyzed by stratifying based on the response at week 14. Results were compared with samples from age- and sex-matched healthy control subjects. RESULTS: Patients receiving induction therapy with IFX (n = 71) or VEDO (n = 51) and healthy control subjects (n = 50) were included. At baseline, hepcidin correlated positively with ferritin and negatively with soluble transferrin receptor/log ferritin index (P < .001). ID was prevalent in 96.7% of patients who had hepcidin levels below the median. Hepcidin accurately identified ID: the area under the curve (hepcidin) was 0.89 (95% confidence interval, 0.82-0.95; P < .001). In total, 75.4% of patients responded to induction therapy; inflammation, hepcidin, and ferritin decreased significantly, while transferrin increased during induction therapy. These changes were observed only in patients who responded to the therapy. CONCLUSIONS: Hepcidin levels in IBD are primarily determined by ID, even in an inflammatory state. In addition, induction therapy can decrease hepcidin levels, which might lead to better bioavailability of iron supplements. Therefore, hepcidin is a potential diagnostic ID biomarker that could assist therapeutic decision making.

Absolute iron deficiency is the primary determinant of hepcidin levels, even in an inflammatory state. Induction therapy can decrease hepcidin levels, which might improve iron bioavailability. Hence, hepcidin is a potential diagnostic iron deficiency biomarker that could assist therapeutic decision making.

Effect of Myofascial Induction Therapy in Pterygoid Muscles of Woodwinds and String Musicians on Muscular Stiffness of the Upper Trapezius.

PURPOSE: Considering the fascial continuity and its biomechanical characteristics, the purpose of this study was to assess the change in muscular stiffness (Dm) of the upper trapezius muscles after the application of myofascial induction therapy (MIT) to the masticatory muscles of musicians. METHODS: This was a pre-posttest design involving one treatment. SUBJECTS: The total sample was 33 subjects (n = 33). The experimental group comprised 18 violin, viola, and woodwind players, and the control group was comprised of 15 non-musicians. The outcome measures included pre-posttest measurements with tensiomyography of the upper trapezius (muscle stiffness, Dm), and baseline neck disability (Neck Disability Index), and pain (SF-36 questionnaire). The experimental group received MIT for 5 minutes on each side of the lateral pterygoid muscle. The control group assumed a supine position for 10 minutes. RESULTS: After the intervention, there was a significant difference in Time per Group (F = 2.896, p = 0.034, ƞ2p = 0.367, and w = 0.755). There were statistically significant differences in pre-post and side-by-side analyses for the Dm of the upper trapezius in the experimental group as well as between the two groups. CONCLUSION: MIT of the lateral pterygoids is effective in decreasing upper trapezius stiffness as measured by an increase in the Dm measured by tensiomyography. The greatest change occurred in musicians with a lower percentage of Neck Disability Index at baseline.

Meta-analysis: efficacy of exclusive enteral nutrition as induction therapy on disease activity index, inflammation and growth factors in paediatric Crohn's disease.

BACKGROUND: There is evidence of inconsistency in sequelae of exclusive enteral nutrition (EEN) as induction therapy in paediatric patients with Crohn's disease (CD). AIM: To investigate the potential effects of EEN on paediatric Crohn's disease activity index (PCDAI), inflammation and biochemical parameters in paediatric patients with CD. METHODS: We performed a comprehensive systematic search of PubMed/MEDLINE, Web of Science, SCOPUS and Embase until 8 January 2022 regardless of the time of publication or language. Random-effects model was applied to combine the datasets. The main outcomes were analysed through mean difference (MD) and its 95% confidence interval (CI). RESULTS: Forty six studies met eligibility criteria and were included in the meta-analysis. Pooled findings indicated that PCDAI score (MD of -27.24; 95% CI -31.84 to -22.64), calprotectin (MD of -842.83 mg/kg; CI -1018.24 to -667.42), CRP (pooled MD of -2.36 mg/dl; CI -2.68 to -2.03), and ESR (MD of -21.09 mm/h; CI -23.79 to -18.38), albumin (MD of 0.65 g/dl; CI 0.58 to 0.72), haemoglobin (MD of 1.12 g/dl; CI 0.87 to 1.37), weight (MD of 4.30 kg; CI 3.39 to 5.22), and height (MD of 0.98 cm; CI 0.35 to 1.62) improved significantly with EEN. CONCLUSIONS: Adherence to EEN can have significant, beneficial effects as induction therapy in paediatric patients with CD.

[Effectiveness of induction therapy with exclusive enteral nutrition in pediatric Crohn's disease]. / å ¨è‚ å† è¥å »å¯¹å„¿ç«¥å ‹ç½—æ©ç— è¯±å¯¼ç¼“è§£ç–—æ•ˆç ”ç©¶.

OBJECTIVES: To evaluate the effectiveness of induction therapy with exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD). METHODS: A retrospective analysis was performed on the medical data of 62 children with CD who received EEN in Children's Hospital, Zhejiang University School of Medicine, from March 2013 to August 2021. The medical data included general information and height, weight, Pediatric Crohn's Disease Activity Index (PCDAI), Crohn's Disease Endoscopic Index of Severity, C-reactive protein, erythrocyte sedimentation rate, and serum albumin level before treatment and after 8 weeks of treatment. The changes in the above indicators were compared before and after treatment. RESULTS: Among the 62 children with CD, there were 39 boys (63%) and 23 girls (37%), with a mean age of (11.9±3.0) years at diagnosis. Among the 55 children who completed EEN treatment for at least 8 weeks, 48 (87%) achieved clinical remission at week 8. PCDAI at week 8 was significantly lower than that before treatment (P<0.001). Except for 17 children with involvement of the small intestine alone and 3 children with involvement of the colon who did not receive colonoscopy reexamination, the remaining 35 children with involvement of the colon received colonoscopy reexamination after the 8-week EEN treatment. Of the 35 children, 29 (83%) achieved mucosal healing. As for the 48 children who achieved clinical remission at week 8, there were significant improvements in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P<0.01). As for the 7 children who did not achieve clinical remission at week 8, there were no significant changes in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P>0.05). CONCLUSIONS: The 8-week EEN treatment has a good effect on clinical remission and mucosal healing in children with CD. For the children with CD achieving clinical remission, EEN can improve their height and body mass index.

6- and 12-Month Outcomes after 90:10 Enteral Nutrition Induction Therapy in Pediatric Crohn's Disease.

OBJECTIVES: Studies describing longer-term outcomes after EEN induction are limited. We describe clinical outcomes during 90:10 EN induction, and 6- and 12- month outcomes among patients that successfully completed EN induction and then continued either EN or immunomodulator (IM) maintenance therapy. METHODS: All children with CD treated with 90:10 EN induction protocol (90% formula:10% regular diet) at our IBD Center from 2013 to 2018 were retrospectively reviewed. Demographic, clinical, and laboratory data were recorded at baseline, 6, and 12 months (± 3 months at each timepoint). Therapy changes after initiation of EN induction through 12 months were recorded. Among patients that successfully completed 90:10 induction, outcomes between EN and IM maintenance groups were compared. RESULTS: In total, 44/105 (42%) patients completed 8-12 weeks of 90:10 EN induction. Sixty-one patients had incomplete EN induction, with 52% requiring corticosteroids and 25% anti-TNF therapy as alternate induction approaches. Forty-four patients completed EN induction (18 continued EN maintenance and 26 IM maintenance therapy). Twenty-seven of these 44 (61%) remained on initial maintenance therapy at 6 months (10/18 (56%) EN and 17/26 (65%) IM). In total, 16/44 (36%) remained on their initial maintenance therapy at 12 months. By 12 months, 10 patients required anti-TNF and 11 corticosteroids after successful completion of induction. CONCLUSIONS: In this retrospective study of short and longer-term outcomes after 90:10 EN induction, the need for an alternate induction therapy was common, most frequently to anti-TNF or corticosteroid therapy. Future studies are needed to evaluate for predictors of long-term success after EN induction.

Exploratory Study of NPC-0501 Trial: Optimal Cisplatin Dose of Concurrent and Induction/Adjuvant Chemotherapy for Locoregionally Advanced Nasopharyngeal Carcinoma.

PURPOSE: The current recommendation for patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is cisplatin-based induction chemotherapy (IC) or adjuvant chemotherapy (AC) plus concurrent chemoradiotherapy (CRT). However, data on the optimal platinum doses for each phase of combined regimens are lacking. EXPERIMENTAL DESIGN: 742 patients with NPC in the NPC-0501 trial treated with CRT plus IC/AC and irradiated with intensity-modulated radiotherapy (IMRT) were analyzed. The optimal platinum dose to achieve the best overall survival (OS) in the concurrent and induction/adjuvant phases was studied. RESULTS: Evaluation of the whole series shows the optimal platinum dose was 160 mg/m2 in the concurrent and 260 mg/m2 in the induction/adjuvant phase. Repeating the analyses on 591 patients treated with cisplatin throughout (no replacement by carboplatin) confirmed the same results. The cohort with optimal platinum doses in both phases had better OS than the cohort suboptimal in both phases (stage III: 90% vs. 75%; stage IVA-B: 80% vs. 56%, at 5-year). Multivariable analyses confirmed optimal platinum doses in both phases versus suboptimal dose in each phase are significant independent factors for OS, with HR of 0.61 [95% confidence interval (CI), 0.41-0.91] and 0.67 (95% CI, 0.48-0.94), respectively. Treatment sequence was statistically insignificant after adjusting for platinum doses. CONCLUSIONS: Both concurrent and IC/AC are needed for locoregionally advanced NPC, even for patients irradiated by IMRT; the concurrent platinum dosage could be set at ≥160 mg/m2 when coupled with adequate induction/adjuvant dosage at ≥260 mg/m2 (or at least ≥240 mg/m2). To achieve these optimal dosages, IC-CRT at conventional fractionation is favored.

AJM300 (carotegrast methyl), an oral antagonist of α4-integrin, as induction therapy for patients with moderately active ulcerative colitis: a multicentre, randomised, double-blind, placebo-controlled, phase 3 study.

BACKGROUND: AJM300 is an oral, small-molecule α4-integrin antagonist. We assessed the efficacy and safety of AJM300 in patients with moderately active ulcerative colitis. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 3 study consisted of two phases: a treatment phase and an open-label re-treatment phase. The study was done at 82 hospitals and clinics in Japan. Patients with a Mayo Clinic score of 6-10, endoscopic subscore of 2 or more, rectal bleeding subscore of 1 or more, and an inadequate response or intolerance to mesalazine were enrolled. Patients were randomly allocated (1:1) via a website to either AJM300 (960 mg) or placebo by the minimisation method, which was adjusted centrally by dynamic assignment against the Mayo Clinic score (≥6 to ≤7, ≥8 to ≤10 points), any use of corticosteroid, anti-TNFα antibody, or immunosuppressants during the disease-active period (yes vs no), duration of induction therapy until randomisation (<4 weeks vs ≥4 weeks) as the minimisation factors. Patients, investigators, site staff, assessors, and the sponsor were masked to treatment assignments. The study drug was administered orally, three times daily, for 8 weeks, and continued for up to 24 weeks if endoscopic remission was not achieved or rectal bleeding did not stop. The primary endpoint was the proportion of patients with a clinical response at week 8, and was analysed in the full analysis set. Clinical response was defined as a reduction in Mayo Clinic score of 30% or more and 3 or more, a reduction in rectal bleeding score of 1 or more or rectal bleeding subscore of 1 or less, and an endoscopic subscore of 1 or less at week 8. The study is registered with ClinicalTrials.gov, NCT03531892, and is closed to recruitment. FINDINGS: Between June 6, 2018, and July 22, 2020, 203 patients were randomly assigned to AJM300 (n=102) or placebo (n=101). At week 8, 46 (45%) patients in the AJM300 group and 21 (21%) patients in the placebo group had a clinical response (odds ratio 3·30, 95% CI 1·73-6·29; p=0·00028). During the 8-week treatment and 16-week extension treatment periods, adverse events occurred in 39 (39%) of 101 patients in the placebo group and 39 (38%) of 102 patients in the AJM300 group. We found no difference in the incidence of adverse events between groups or after repeated administration of AJM300. The most common adverse event was nasopharyngitis (11 [11%] of 101 patients in the placebo group and ten [10%] of 102 patients in the AJM300 group). The most common treatment-related adverse event was also nasopharyngitis (four [4%] of 101 patients in the placebo group and three [3%] of 102 patients in the AJM300 group). Most adverse events were mild-to-moderate in severity. No deaths were reported. A serious adverse event was reported in the AJM300 group (one patient with anal abscess), but this was judged to be unrelated to study drug. INTERPRETATION: AJM300 was well tolerated and induced a clinical response in patients with moderately active ulcerative colitis who had an inadequate response or intolerance to mesalazine. AJM300 could be a novel induction therapy for the treatment of patients with moderately active ulcerative colitis. FUNDING: EA Pharma and Kissei Pharmaceutical. TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

Survival After Induction Chemotherapy and Chemoradiation Versus Chemoradiation and Adjuvant Chemotherapy for Locally Advanced Rectal Cancer.

BACKGROUND: Total neoadjuvant therapy (TNT) improves tumor response in locally advanced rectal cancer (LARC) patients compared to neoadjuvant chemoradiotherapy alone. The effect of TNT on patient survival has not been fully investigated. MATERIALS AND METHODS: This was a retrospective case series of patients with LARC at a comprehensive cancer center. Three hundred and eleven patients received chemoradiotherapy (chemoRT) as the sole neoadjuvant treatment and planned adjuvant chemotherapy, and 313 received TNT (induction fluorouracil and oxaliplatin-based chemotherapy followed by chemoradiotherapy in the neoadjuvant setting). These patients then underwent total mesorectal excision or were entered in a watch-and-wait protocol. The proportion of patients with complete response (CR) after neoadjuvant therapy (defined as pathological CR or clinical CR sustained for 2 years) was compared by the χ2 test. Disease-free survival (DFS), local recurrence-free survival, distant metastasis-free survival, and overall survival were assessed by Kaplan-Meier analysis and log-rank test. Cox regression models were used to further evaluate DFS. RESULTS: The rate of CR was 20% for chemoRT and 27% for TNT (P=.05). DFS, local recurrence-free survival, metastasis-free survival, and overall survival were no different. Disease-free survival was not associated with the type of neoadjuvant treatment (hazard ratio [HR] 1.3; 95% confidence interval [CI] 0.93-1.80; P = .12). CONCLUSIONS: Although TNT does not prolong survival than neoadjuvant chemoradiotherapy plus intended postoperative chemotherapy, the higher response rate associated with TNT may create opportunities to preserve the rectum in more patients with LARC.

Application of myofascial induction therapy in the rehabilitation of patients with acute facial palsy: A nonrandomized controlled trial.

BACKGROUND: In the healthy body, the fascial system maintains elasticity and coordination of movements. If these functions are destroyed, facial paraly appears. Myofascial induction therapy (MIT), a manual physical therapy method that focuses on restoring altered fascial tissue, is prevalently and widely used in clinical treatment. OBJECTIVE: The study aimed to observe the application of MIT in the rehabilitation of patients with acute facial palsy. METHODS: Sixty-eight patients with acute facial palsy were divided into control group and manual treatment group. The control group received drug treatments, such as prednisone, methylcobalamin, and vitamin B1, and instrumental physical therapy, such as semiconductor laser, shortwave therapy, and facial muscle training. In addition to these treatments, the manual treatment group received MIT. Both groups were treated for 4 weeks. The patients were assessed using the following methods: the House-Brackmann facial nerve function evaluation, Sunnybrook facial grading system, facial nerve electrophysiological examination compound muscle action potential (CMAP) amplitude, and blink reflex (BR) R1 latency. RESULTS: House-Brackmann and Sunnybrook scores and CMAP amplitude and BRR1 latencies were significantly different between the two groups (p < 0.05). Furthermore, the manual treatment group showed greater improvement than the control group (p < 0.05). CONCLUSIONS: Treatment with MIT promoted better recovery of acute facial palsy and thus may be considered a valid rehabilitation intervention that is worthy of clinical application.

Early discontinuation of induction therapy in chemoimmunotherapy as an effective alternative to the standard regimen in patients with non-small cell lung cancer: a retrospective study.

PURPOSE: We aimed to investigate whether induction chemotherapy with less than four courses is as effective as induction chemotherapy with more than four courses in non-small cell lung cancer (NSCLC) patients receiving chemoimmunotherapy. METHODS: We retrospectively enrolled 249 patients with NSCLC who received chemoimmunotherapy at 12 centers in Japan between January and December 2019. The patient group that completed less than four courses owing to adverse events (AEs), and received subsequent maintenance therapy was compared to the group that received at least four courses of induction chemotherapy followed by maintenance therapy. RESULTS: On univariate and multivariate analyses, the patient group that transitioned to maintenance therapy after completing less than four courses of induction chemotherapy had significantly shorter progression-free survival (PFS) than those who completed at least four courses (hazard ratio [HR] 2.15, 95% confidence interval: 1.38-3.37, p < 0.001 and HR 2.32, 95% confidence interval: 1.40-3.84, p = 0.001, respectively). There was no obvious difference in PFS between the group in which induction chemotherapy ended in two or three courses leading to partial or complete response, and the group that continued at least four courses of induction chemotherapy (log-rank test p = 0.53). CONCLUSION: Treatment efficacy may be maintained if induction chemotherapy is completed in less than four courses owing to development of AEs, and is administered for more than two courses with partial or complete response; efficacy is maintained even on transitioning to maintenance therapy.

Radiation therapy of pancreatic cancers.

We present the update of the recommendations of the French society of oncological radiotherapy on radiotherapy of pancreatic tumors. Currently, the use of radiation therapy for patients with pancreatic cancer is subject to discussion. In the adjuvant setting, the standard treatment is six months of chemotherapy with 5-fluorouracile, irinotecan and oxaliplatin. Chemoradiation may improve the survival of patients with incompletely resected tumours (R1). This remains to be confirmed by a prospective trial. Neoadjuvant chemoradiation is a promising treatment especially for patients with borderline resectable tumours. For patients with locally advanced tumours, there is no standard. An induction chemotherapy followed by chemoradiation for non progressive patients reduces the rate of local relapse. Whereas in the first trials of chemoradiation large fields were used, the treated volumes have been reduced to improve tolerance. Tumour movements induced by breathing should be taken in account. Intensity modulated radiation therapy allows a reduction of doses to the organs at risk. Whereas widely used, this technique has poor evidence-based recommendation. Stereotactic body radiation therapy is also being studied, as a neoadjuvant or exclusive treatment.

Effectiveness of induction therapy with exclusive enteral nutrition in pediatric Crohn's disease / 中国当代儿科杂志

OBJECTIVES@#To evaluate the effectiveness of induction therapy with exclusive enteral nutrition (EEN) in pediatric Crohn's disease (CD).@*METHODS@#A retrospective analysis was performed on the medical data of 62 children with CD who received EEN in Children's Hospital, Zhejiang University School of Medicine, from March 2013 to August 2021. The medical data included general information and height, weight, Pediatric Crohn's Disease Activity Index (PCDAI), Crohn's Disease Endoscopic Index of Severity, C-reactive protein, erythrocyte sedimentation rate, and serum albumin level before treatment and after 8 weeks of treatment. The changes in the above indicators were compared before and after treatment.@*RESULTS@#Among the 62 children with CD, there were 39 boys (63%) and 23 girls (37%), with a mean age of (11.9±3.0) years at diagnosis. Among the 55 children who completed EEN treatment for at least 8 weeks, 48 (87%) achieved clinical remission at week 8. PCDAI at week 8 was significantly lower than that before treatment (P<0.001). Except for 17 children with involvement of the small intestine alone and 3 children with involvement of the colon who did not receive colonoscopy reexamination, the remaining 35 children with involvement of the colon received colonoscopy reexamination after the 8-week EEN treatment. Of the 35 children, 29 (83%) achieved mucosal healing. As for the 48 children who achieved clinical remission at week 8, there were significant improvements in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P<0.01). As for the 7 children who did not achieve clinical remission at week 8, there were no significant changes in height-for-age Z-score and body mass index-for-age Z-score at week 8 (P>0.05).@*CONCLUSIONS@#The 8-week EEN treatment has a good effect on clinical remission and mucosal healing in children with CD. For the children with CD achieving clinical remission, EEN can improve their height and body mass index.

Is there an optimal adjunct therapy to traditional cytotoxic induction?

The traditional cytotoxic induction regimen for acute myeloid leukemia (AML) is seven days of standard-dose cytarabine and three days of an anthracycline antibiotic (such as daunorubicin or idarubicin), commonly known as "7 + 3." Many studies have been conducted to find an additional agent that might improve efficacy. Data from select studies has shown, in certain populations, benefit to adding cladribine, clofarabine and lomustine to a traditional backbone. For mutation-based chemotherapy regimens, midostaurin with 7 + 3 is the current standard of care for FLT3-mutant, younger AML patients. As we learn more about the synergism of molecular agents and traditional anti-cancer treatments, we can hopefully develop novel regimens without abandoning some of the benefits of these mutation agnostic historical therapies.

Levocarnitine for pegaspargase-induced hepatotoxicity in older children and young adults with acute lymphoblastic leukemia.

BACKGROUND: Pegaspargase (PEG-ASP) is an integral component of therapy for acute lymphoblastic leukemia (ALL) but is associated with hepatotoxicity that may delay or limit future therapy. Obese and adolescent and young adult (AYA) patients are at high risk. Levocarnitine has been described as potentially beneficial for the treatment or prevention of PEG-ASP-associated hepatotoxicity. METHODS: We collected data for patients age ≥10 years who received levocarnitine during induction therapy for ALL, compared to a similar patient cohort who did not receive levocarnitine. The primary endpoint was conjugated bilirubin (c.bili) >3 mg/dl. Secondary endpoints were transaminases >10× the upper limit of normal and any Grade ≥3 hepatotoxicity. RESULTS: Fifty-two patients received levocarnitine for prophylaxis (n = 29) or rescue (n = 32) of hepatotoxicity. Compared to 109 patients without levocarnitine, more patients receiving levocarnitine were obese and/or older and had significantly higher values for some hepatotoxicity markers at diagnosis and after PEG-ASP. Levocarnitine regimens varied widely; no adverse effects of levocarnitine were identified. Obesity and AYA status were associated with an increased risk of conjugated hyperbilirubinemia and severe transaminitis. Multivariable analysis identified a protective effect of levocarnitine on the development of c.bili >3 mg/dl (OR 0.12, p = 0.029). There was no difference between groups in CTCAE Grade ≥3 hepatotoxicity. C.bili >3 mg/dl during induction was associated with lower event-free survival. CONCLUSIONS: This real-world data on levocarnitine supplementation during ALL induction highlights the risk of PEG-ASP-associated hepatotoxicity in obese and AYA patients, and hepatotoxicity's potential impact on survival. Levocarnitine supplementation may be protective, but prospective studies are needed to confirm these findings.

Organ Preservation in Patients with Rectal Cancer Treated with Total Neoadjuvant Therapy.

BACKGROUND: Retrospective studies suggest that watch-and-wait is a safe alternative to total mesorectal excision in selected patients with a clinical complete response after chemoradiotherapy. OBJECTIVE: This study aimed to determine the proportion of patients with rectal cancer who may benefit from watch-and-wait. DESIGN: This study is a retrospective analysis of data from prospectively maintained databases. SETTING: This study was conducted at a comprehensive cancer center. PATIENTS: Consecutive patients with stage II or III rectal adenocarcinoma who were treated with total neoadjuvant therapy using induction chemotherapy between 2012 and 2019 under the care of the same surgeon were included. INTERVENTION: Induction-type total neoadjuvant therapy consisted of 8 cycles of leucovorin-fluorouracil-oxaliplatin or 5 cycles of capecitabine-oxaliplatin before chemoradiotherapy. Patients with a clinical complete response were offered watch-and-wait, and patients with residual tumor were offered total mesorectal excision. MAIN OUTCOMES AND MEASURES: Tumor response was assessed with a digital rectal examination, endoscopy, and MRI. Patient characteristics and recurrence-free survival were compared between the watch-and-wait group and the total mesorectal excision group. RESULTS: A total of 88 patients were included in the analysis. One (1%) died during neoadjuvant therapy. Fifty-five patients (62.5%) had an incomplete clinical response and underwent surgery, 10 (18%) of the 55 developed distant metastasis, and 3 (5%) developed local recurrence. The remaining 32 patients (36.3%) had a clinical complete response and underwent watch-and-wait. On average, patients in the watch-and-wait group were older and had smaller, more distal tumors compared with patients in the surgery group. The median radiation dose, number of chemotherapy cycles, rate of adverse events, and length of follow-up did not differ substantively between the total mesorectal excision group and the watch-and-wait group. In the watch-and-wait group, 2 (6%) patients developed tumor regrowth, and one of them had distant metastasis. Recurrence-free survival was significantly higher in the watch-and-wait group. LIMITATIONS: Generalizability, sample size, and follow-up duration were limitations of this study. CONCLUSIONS: Approximately one-third of patients with stage II or III rectal cancer can benefit from a watch-and-wait approach with the aim of preserving the rectum if treated with induction-type total neoadjuvant therapy and followed by an experienced multidisciplinary team. See Video Abstract at http://links.lww.com/DCR/B688. CONSERVACIN DE RGANOS EN PACIENTES CON CNCER DE RECTO TRATADOS CON TERAPIA NEOADYUVANTE TOTAL: ANTECEDENTES:Estudios retrospectivos sugieren que observar y esperar es una alternativa segura a la escisión mesorrectal total en pacientes seleccionados con una respuesta clínica completa después de la quimiorradioterapia.OBJETIVO:Determinar la proporción de pacientes con cáncer de recto que pueden beneficiarse de observar y esperar.DISEÑO:Análisis retrospectivo de datos de bases de datos mantenidas de forma prospectiva.ESCENARIO:Centro Oncológico Integral.PACIENTES:Pacientes consecutivos con adenocarcinoma de recto en estadio II o III tratados con TNT utilizando quimioterapia de inducción entre 2012 y 2019 bajo el cuidado del mismo cirujano.INTERVENCIÓN:La terapia neoadyuvante total de tipo inducción consistió en ocho ciclos de leucovorín-fluorouracilo-oxaliplatino o cinco ciclos de capecitabina-oxaliplatino antes de la quimiorradioterapia. A los pacientes con una respuesta clínica completa se les ofreció observar y esperar, y a los pacientes con tumor residual se les ofreció la escisión mesorrectal total.PRINCIPALES RESULTADOS Y MEDIDAS:La respuesta del tumor se evaluó con un tacto rectal, endoscopia y resonancia magnética. Se compararon las características de los pacientes y la supervivencia libre de recurrencia entre el grupo de observación y espera y el grupo de escisión mesorrectal total.RESULTADOS:Se incluyó en el análisis a un total de 88 pacientes. Uno (1%) murió durante la terapia neoadyuvante. Cincuenta y cinco pacientes (62.5%) tuvieron una respuesta clínica incompleta y se sometieron a cirugía; 10 (18%) de los 55 desarrollaron metástasis a distancia y 3 (5%) desarrollaron recidiva local. Los 32 pacientes restantes (36.3%) tuvieron una cCR (respuesta clínica completa) y se sometieron a observar y esperar. En promedio, los pacientes del grupo de observación y espera eran mayores y tenían tumores más pequeños y distales en comparación con el grupo de cirugía. La dosis mediana de radiación, el número de ciclos de quimioterapia, la tasa de eventos adversos y la duración del seguimiento no difirieron sustancialmente entre el grupo de escisión mesorrectal total y el grupo de observación y espera. En el grupo de observación y espera, 2 (6%) pacientes desarrollaron recrecimiento del tumor y uno de ellos tuvo metástasis a distancia. La supervivencia libre de recurrencia fue significativamente mayor en el grupo de observación y espera.LIMITACIONES:Generalizabilidad, tamaño de la muestra, duración del seguimiento.CONCLUSIONES:Aproximadamente un tercio de los pacientes con cáncer de recto en estadio II o III pueden beneficiarse de un abordaje de observación y espera con el objetivo de preservar el recto si se tratan con terapia neoadyuvante total de tipo inducción y son seguidos por un equipo multidisciplinario experimentado. Consulte Video Resumen en http://links.lww.com/DCR/B688.