Return to Intended Oncological Therapy: State of the Art and Perspectives.

PURPOSE OF THE REVIEW: Despite advances in surgical procedures, cancer recurrence still affects a substantial proportion of patients for whom surgery is considered a curative therapy. This review aims to provide a comprehensive overview of RIOT, addressing its definition, influencing factors, and clinical implications. FINDINGS: RIOT can be defined as a continuous variable as the time from surgery to initiation of adjuvant therapies or categorically as whether patients can successfully receive adjuvant therapies or not. Factors influencing RIOT are age, sex, socioeconomic status, access to healthcare, physical performance and comorbidities, and quality of anesthesia and surgical care. Adjuvant therapies such as chemotherapy, radiotherapy, and immunotherapy are often administered to reduce the risk of recurrence after surgery and improve survival. Return to intended oncologic therapy (RIOT) has emerged as a promising outcome metric reflecting patients' functional recovery after surgery and their ability to receive adjuvant therapies.

A randomized study of 6 versus 3 years of adjuvant imatinib in patients with localized GIST at high risk of relapse.

BACKGROUND: The administration of adjuvant imatinib during 3 years is indicated after resection of primary localized GIST at high risk of recurrence, but many patients relapse afterwards. METHODS: IMADGIST (NCT02260505) was a multicenter, open-label, randomized phase III study evaluating the maintenance of imatinib for 3 more years (6-year arm) compared with interruption (3-year arm) from the day of randomization, conducted in the French Sarcoma Group. The primary endpoint was intent-to-treat disease-free survival. Secondary endpoints included overall survival, time to imatinib resistance, response after imatinib reintroduction at relapse, and safety. RESULTS: From 24 December 2014 to 4 April 2023, 136 patients aged ≥18 years, Eastern Cooperative Oncology Group performance status ≤2, with a localized gastrointestinal stromal tumor with an R0 or R1 surgery, and a risk of tumor recurrence ≥35% according to National Comprehensive Cancer Network (NCCN) risk classification were randomized in 14 centers. Sixty-five patients were randomized to the 3-year arm versus 71 to the 6-year arm. There were 68 males and females. Primary sites were gastric and small bowel in 60 (44%) and 64 (47%) patients, respectively. Respectively, 52 (38%) and 71 (52%) patients had a risk of relapse of 35%-70% and >70%. With a median follow-up of 55 months (interquartile range 46-59 months) after randomization, disease-free survival was significantly superior in the 6-year arm [hazard ratio: 0.40 (0.20-0.69), P = 0.0008]. Time to imatinib resistance, survival, adverse events, and quality of life were not different in the two arms. CONCLUSIONS: Three additional years of adjuvant imatinib reduces the risk of relapse in patients who have received 3 years of adjuvant imatinib with an acceptable tolerance.

Treatment Patterns and Outcomes of Stage III Melanoma Patients with Positive Sentinel Lymph Node Biopsy: A Real-Life Experience.

Background: Advancements in managing stage III melanoma have involved the implementation of adjuvant therapies alongside a simultaneous decrease in the utilization of completion lymph node dissection (CLND) following positive sentinel node biopsy (SLNB). Methods: This retrospective study from the University of Turin's Dermatology Clinic analyzed relapse-free survival (RFS) and overall survival (OS) among stage III melanoma patients (n = 157) who underwent CLND after positive SLNB versus those who did not receive such procedure. Results: Patients without CLND had a median RFS of 49 months (95% CI 42-NA), while CLND recipients showed 51 months (95% CI 31-NA) (p = 0.139). The 48-month OS for non-CLND patients was 79.8% (95% CI 58.2-91.0) versus 79.2% (95% CI 67.5-87.0) for CLND recipients (p = 0.463). Adjusted Hazard Ratios through inverse probability treatment weighting revealed the impact of CLND to be insignificant on RFS (aHR 0.90, 95% CI 0.37-2.22) and marginal on OS (aHR 0.41, 95% CI 0.13-1.21). Conversely, adjuvant therapy significantly reduced the risk of relapse (aHR 0.46, 95% CI 0.25-0.84), irrespective of CLND. Conclusions: This study corroborates the growing evidence that CLND after positive SLNB does not enhance RFS or OS, while emphasizing the crucial role of adjuvant therapy, be it immunotherapy or targeted therapy, in reducing the risk of relapse in melanoma patients with positive SLNB.

One-Year Analysis of Autologous Peripheral Blood Mononuclear Cells as Adjuvant Therapy in Treatment of Diabetic Revascularizable Patients Affected by Chronic Limb-Threatening Ischemia: Real-World Data from Italian Registry ROTARI.

Wounds in diabetic patients with peripheral arterial disease (PAD) may be poorly responsive to revascularization and conventional therapies. Background/Objective: This study's objective is to analyze the results of regenerative cell therapy with peripheral blood mononuclear cells (PBMNCs) as an adjuvant to revascularization. Methods: This study is based on 168 patients treated with endovascular revascularization below the knee plus three PBMNC implants. The follow-up included clinical outcomes at 1-2-3-6 and 12 months based on amputations, wound healing, pain, and TcPO2. Results: The results at 1 year for 122 cases showed a limb rescue rate of 94.26%, a complete wound healing in 65.59% of patients, and an improvement in the wound area, significant pain relief, and increased peripheral oxygenation. In total, 64.51% of patients completely healed at 6 months, compared to the longer wound healing time reported in the literature in the same cohort of patients, suggesting that PBMNCs have an adjuvant effect in wound healing after revascularization. Conclusions: PBMNC regenerative therapy is a safe and promising treatment for diabetic PAD. In line with previous experiences, this registry shows improved healing in diabetic patients with below-the-knee arteriopathy. The findings support the use of this cell therapy and advocate for further research.

Real-World Evidence of Adjuvant Immunotherapy in Resected Stage III and IV Melanoma Patients: CADIM Trial Final Results. Experience from 2 Tertiary Referral Centers. / Evidencia en la práctica clínica del tratamiento adyuvante con inmunoterapia en pacientes con melanoma en estadios III y IV resecados: resultados finales del estudio CADIM. Experiencia de 2centros de tercer nivel.

INTRODUCTION: Clinical trials have validated the use of nivolumab and pembrolizumab as adjuvant therapies regarding relapse-free survival in patients with resected stage III and IV melanoma. Evidence in real-world patients is currently limited. MATERIAL AND METHOD: The CADIM trial (Characterization of adjuvant immunotherapy in melanoma patients) recruited a total of 81 patients with resected stage III and IV melanoma on nivolumab or pembrolizumab as adjuvant therapy from February 2018 through December 2022. RESULTS: The stage distribution rate was 81.5% (n=71) for stage III, while 15 patients (18.5%) had resected stage IV. Among stage III patients, 38 were stage IIIC (46.9%). With a median follow-up of 22.8 months, the relapse-free survival in the intention-to-treat population was 84% at one year and 81.5% at 2 years. The overall survival rate was 99% at one year and 91.4% at 2 years. Grade 3-4 treatment-related adverse events were reported in 12.3% of the patients. CONCLUSIONS: This study shows the results of resected stage III and IV melanoma patients on adjuvant therapy with anti-PD-1, and eventually confirmed the safety and efficacy profile described by clinical trials. Comparing clinical trial data with real-world evidence is necessary for a more practical, reliable, and accessible use of these drugs.

Surgery-based radiation-free multimodality treatment for locally advanced cervical cancer.

The current review described a 55-year woman using 28 months to finish her surgery-based radiation-free multimodality treatment journey to fight International Federation of Gynaecology & Obstetrics (FIGO) 2018 clinical stage IIA2 (cT2aN0M0) squamous cell carcinoma (SCC) of the cervix. She received six cycles of perioperative adjuvant therapy, including three cycles of neoadjuvant therapy (NAT) and three cycles of postoperative adjuvant therapy by using combination of dose-dense chemotherapy (CT, weekly paclitaxel 80 mg/m2+triweekly cisplatin 40 mg/m2), immunotherapy (IO, triweekly pembrolizumab 200 mg) and half-dose anti-angiogenic agent (triweekly bevacizumab 7.5 mg/kg) plus interval radical surgery (radical hysterectomy + bilateral salpingo-oophorectomy + bilateral pelvic lymph node dissection + para-aortic lymph node sampling) and following maintenance therapy with monthly 22 cycles of half-dose of IO (pembrolizumab 100 mg) and concomitant 4 cycles of single-agent CT (paclitaxel 175 mg/m2) and 18 cycles of half-dose anti-angiogenic agent (bevacizumab 7.5 mg/kg). During the cervical SCC fighting journey, two unwanted adverse events (AEs) occurred. One was pseudo-progressive disease during the NAT treatment and pathology-confirmed upgrading FIGO stage IIIC1p (ypT2a1N1M0) after radical surgery and the other was the occurrence of hypothyroidism during the post operative adjuvant therapy. Based on this case we presented, we review the recent trend in the management of women with locally advanced cervical cancer (LACC) using the radiation-free but surgery-based multimodality strategy and highlight the strengths and limitations about perioperative adjuvant therapy with dose-dense CT + IO + half-dose anti-angiogenic agent and maintenance treatment of half-dose IO combining with short-term single agent CT and following long-term half-dose anti-angiogenic agent. All underscore the possibility that women with LACC have an opportunity to receive surgery-based RT-free multi-modality strategy to manage their diseases with satisfactory results. Additionally, the evolving role of IO plus CT with/without anti-angiogenic agent functioning as either primary treatment or adjuvant therapy for the treatment of advanced CC has been in process continuously. Moreover, the patient's positive response to IO, pembrolizumab as an example, both during the primary and maintenance therapy, highlights the importance of integrating IO into CT regimens for CC, especially in cases where conventional therapies, RT as an example, are insufficient or who do not want to receive RT-based treatment. The sustained disease-free status of the patient over several years reinforces the potential of IO to significantly increase long-term survival outcomes in CC patients, particularly for those with LACC.

Disparities in postoperative adjuvant therapy utilization and factors impacting survival among anaplastic thyroid cancer patients.

BACKGROUND: Anaplastic thyroid cancer (ATC) is highly aggressive with a poor prognosis. Adjuvant systemic therapy and radiation post-surgery are endorsed by NCCN and ATA guidelines. Our study aimed to identify those at risk of forgoing postoperative adjuvant treatment and to determine survival predictors. METHODS: We used the National Cancer Database (NCDB) to identify ATC patients who underwent upfront thyroidectomy from 2010 to 2017, excluding those opting for palliative care. We compared demographics, characteristics, treatments, and outcomes between those who received adjuvant therapy and those who did not. Predictors of receiving adjuvant therapy were identified using logistic regression, while Cox regression identified survival factors. RESULTS: Of 563 patients, 160 received no adjuvant treatment, 82 received radiation only, 16 received systemic therapy only, and 305 received combination therapy. Notably, over 75 â€‹% of patients who did not receive adjuvant treatment had it excluded from their treatment plan, not due to refusal. Older age (OR 0.92) and non-white race/ethnicity (OR 0.33) were significant predictors of not receiving adjuvant therapy. Undergoing a total thyroidectomy, an R0 or R1 resection, and radiation or combination therapy were associated with better survival, while non-metropolitan location, primary tumor size >7.5 â€‹cm, and stage IVC disease were negative factors. CONCLUSION: Total thyroidectomy, R0/R1 resection, and adjuvant therapy reduce mortality in ATC patients. However, older patients and minorities are less likely to receive adjuvant therapy, underscoring disparities in treatment adherence.

Adjuvant therapy and recurrence risk in non-myoinvasive high-grade (stage IC) endometrial cancer: A systematic review and meta-analysis.

OBJECTIVE: To summarize practice patterns and outcomes among patients with non-myoinvasive high-grade (formerly stage IA, now stage IC) endometrial cancer. METHODS: We conducted a systematic search using MEDLINE, Embase, Cochrane, Web of Science, and ClinicalTrials.gov databases from inception to May 8, 2024 to identify studies reporting on treatment and outcomes of non-myoinvasive high-grade endometrial cancer. We included full-text English reports of patients undergoing adjuvant therapy or surveillance for polyp- or endometrium-confined high-grade endometrial cancer without myometrial invasion containing data on recurrence or survival outcomes. Two reviewers independently screened studies; a third reviewer resolved disagreements. Data were extracted using a standardized form. The primary outcome was recurrence risk. Random-effects meta-analysis was used to summarize binomial proportions and to compare outcomes by adjuvant treatment strategy. RESULTS: A total of 29 studies were included, representing 2770 unique patients. Overall, 49.0 % of patients were managed with observation and 37.9 % with chemotherapy. Most patients (92.5 %) had serous histology. Of 23 studies with data on recurrence, 13.7 % of patients recurred, with a meta-analysis estimate recurrence risk of 11 % (95 % confidence interval [CI]: 8-15 %). Across 13 studies reporting on recurrence by receipt of chemotherapy versus no chemotherapy, comparative meta-analysis showed similar likelihood of recurrence (8.0 % versus 13.2 %; odds ratio 0.73, 95 % CI: 0.38-1.42). Comparative meta-analyses for (1) adjuvant therapy versus observation and (2) observation or vaginal brachytherapy versus chemotherapy and/or external beam radiation therapy demonstrated no statistically significant difference in recurrence risk. Sensitivity analyses results, including those limiting to studies of patients with serous histology (12 studies) or complete surgical staging (10 studies), were overall consistent with the primary analysis. Survival data was inconsistently reported and not amenable to meta-analysis. CONCLUSION: Among patients with non-myoinvasive high-grade endometrial cancer, recurrence risk was 11 % and use of adjuvant therapy was not associated with reduced recurrence risk. Prospective study of this population is warranted.

Impact of post-operative transoral robotic surgery hemorrhage on adjuvant treatment delays in patients with oropharyngeal squamous cell carcinoma.

OBJECTIVES: Transoral robotic surgery (TORS) for the treatment for oropharyngeal squamous cell carcinoma (SCC) carries a risk of post-operative hemorrhage. Increased time from surgery to completion of adjuvant therapy has been associated with decreased survival. Our objective was to assess for adjuvant treatments delays in patients with post-operative bleeding. Secondarily, to assess post-operative swallowing outcomes. MATERIALS AND METHODS: Retrospective chart review of all patients who underwent TORS from 2014 to 2021 at a tertiary care center. Patient demographics, adjuvant therapy course, treatment-related dysphagia outcomes, incidence and severity of post-operative bleeding were reviewed. RESULTS: 221 patients underwent TORS, 160 (72%) of which were recommended to undergo adjuvant treatment. 33 patients developed post-operative bleeding, of which 22 patients underwent at least partial radiation therapy (RT) where there was an average of 53.0 ± 12 days elapsed from surgery to the initiation of RT. In the control group, 124 completed at least partial adjuvant treatment and there was an average of 55.3 ± 23 days from surgery to start of adjuvant RT. Time to start of RT was not significantly different between the cohorts (p=0.47). 9.1% of patients with bleeding and 23.7% of those without bleeding started radiation therapy within 6 weeks. The odds ratio of requiring a feeding tube during treatment in patients with post-operative bleeding compared to those without was 1.3 (95% C.I. 0.54-3.13). CONCLUSION: Patients with post-operative bleeding following TORS with TAL were not found to have a significantly higher risk of treatment delays or dysphagia burden, independent of hemorrhage severity.

Motor improvement in Parkinson's disease patients receiving caffeine adjuvants: A double-blind randomized controlled trial in Indonesia.

Parkinson's disease (PD) manifests as a movement and brain function disorder characterized by symptoms such as resting tremors, rigidity, bradykinesia, and postural instability, leading to disability among patients. The use of psychostimulants such as caffeine has been associated with the improvement of motor symptoms in PD patients; however, studies regarding the effect of caffeine adjuvant therapy on motor function among PD patients in the Indonesian population are lacking. The aim of this study was to evaluate motor improvement as measured by the change in scores of the Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) among PD patients receiving caffeine adjuvant. A double-blind randomized controlled trial (RCT) was conducted among PD patients at Dr. Soetomo General Academic Hospital and Universitas Airlangga Hospital, Surabaya, Indonesia, from April to August 2023. A total of 27 patients were enrolled and randomly assigned to an intervention (receiving caffeine adjuvant, n=15) and control group (receiving placebo, n=12). Motor improvement was measured using the UPDRS III score prior to intervention and three weeks after. The Chi-squared test was used to analyze the difference in UPDRS III scores between the two groups. Motor improvement, as demonstrated by a reduction in the UPDRS III score, was observed in patients receiving caffeine adjuvant compared to those receiving placebo (80.0% vs 16.7%; p=0.004). Regarding the safety profile, only four out of 15 (26.6%) patients treated with caffeine reported minor adverse events. These conditions improved over time during the intervention. None of the 12 patients in the placebo reported adverse events. This study provides valuable insights into the initial dosage of caffeine that improves motor function in PD patients with minimum adverse effects.

Navigating precision: the crucial role of next-generation sequencing recurrence risk assessment in tailoring adjuvant therapy for hormone receptor-positive, human epidermal growth factor Receptor2-negative early breast cancer.

Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer is the most common subtype, representing over two-thirds of new diagnoses. Adjuvant therapy, which encompasses various medications and treatment durations, is the standard approach for managing early stage HR+ HER2- breast cancer. Optimizing treatment is essential to minimize unnecessary side effects while addressing the biological variability inherent in HR+/HER2- breast cancers. Incorporating biological biomarkers into treatment decisions, alongside traditional clinical factors, is vital. Gene expression assays can identify patients unlikely to benefit from adjuvant chemotherapy, thereby refining treatment strategies and improving risk assessment. This paper reviews evidence for several genomic tests, including Oncotype DX, MammaPrint, Breast Cancer Index, RucurIndex, and EndoPredict, which assist in tailoring adjuvant therapy. Additionally, we explore the role of liquid biopsies in personalizing treatment, emphasizing the importance of considering late relapse risks and potential benefits of extended systemic therapy for HR+/HER2- breast cancer patients.

Effects of Nicotinamide Adenine Dinucleotide on Older Patients with Heart Failure.

Background: Heart failure (HF) is the main cause of death in middle-aged and older people and is characterized by high morbidity, high mortality, a high rehospitalization rate, and many high-risk groups. Nicotinamide adenine dinucleotide (NAD+) is widely present in the mitochondria of cardiomyocytes and maintains the redox balance in the body, which can effectively treat HF. We sought to evaluate whether NAD+ therapy has some clinical efficacy in patients with HF. Methods: Based on using conventional drugs to treat HF, patients (n = 60) were randomized 1:1 to saline and 50 mg NAD+ with 50 mL of normal saline for 7 days. The baseline characteristics of patients before and after treatment and cardiac function (N-terminal pro B-type natriuretic peptide (NT-proBNP) level and left ventricular ejection fraction (LVEF) value) were analyzed. Serological analysis (sirtuin-1 (SIRT1), sirtuin-3 (SIRT3), sirtuin-6 (SIRT6), reactive oxygen species (ROS), and endothelin) was also performed. Results: Among the 60 patients with HF who were treated with NAD+ for 7 days, the improvement rate in NT-proBNP levels and LVEF values was better than in the saline group, although not statistically significant. These patients were more likely to benefit from NAD+ because of higher levels of anti-oxidative stress (SIRT1, SIRT3, SIRT6, and ROS) and anti-endothelial injury (endothelin) than those in the saline control group. Conclusions: According to the results of this study, it is believed that 7 days of NAD+ injections has a positive effect on improving cardiac function, oxidative stress, and endothelial injury in patients with HF compared with the saline control. Clinical Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/) ChiCTR2300074326; retrospectively registered on 3 August 2023.

The impact of postoperative adjuvant therapy on EGFR-mutated stage IA lung adenocarcinoma with micropapillary pathological subtypes.

BACKGROUND: Micropapillary (MPP) adenocarcinoma is considered one of the most aggressive pathological types of lung adenocarcinoma (LADC). This retrospective study aimed to evaluate the prognostic significance and benefit of postoperative adjuvant therapy (PAT) in stage IA LADC patients with different proportions of MPP components. MATERIALS AND METHODS: We retrospectively examined clinical stage IA LADC patients who underwent surgical resection between August 2012 and December 2019. In terms of the proportion of MPP components (TPM), the tumors were reclassified into three categories: MPP patterns absent (TPMN); low proportions of MPP components (TPML); and high proportions of MPP components (TPMH). The dates of recurrence and metastasis were identified based on physical examinations and were confirmed by histopathological examination. RESULTS: Overall, 505 (TPMN, n = 375; TPML, n = 92; TPMH, n = 38) patients harboring EGFR mutations were enrolled in the study. Male sex (P = 0.044), high pathological stage (P < 0.001), and MPP pathological subtype (P < 0.001) were more frequent in the TPM-positive (TPMP) group than in the TPM-negative (TPMN) group. Five-year disease-free survival (DFS) rates were significantly lower in the TPMP group than in the TPMN group (84.5% vs. 93.4%, P = 0.006). In addition, patients with high proportions (greater than 10%) of MPP components had worse overall survival (OS) (91.0% vs. 98.9%, P = 0.025) than those with low proportions (5%≤ TPM ≤ 10%). However, postoperative EGFR tyrosine kinase inhibitors (TKIs) or adjuvant chemotherapy (ACT) cannot improve DFS and OS between EGFR-mutated patients with different proportions of MPP components. CONCLUSION: MPP was related to earlier recurrence and shortened survival time, even in stage IA. Further research needs a larger sample size to clarify that EGFR-mutated stage IA patients with MPP components obtain survival benefits from adjuvant therapy.

[Classical chemotherapy, immunotherapy, or adjuvant radiotherapy-how to improve the oncologic outcome of radical cystectomy?] / Klassische Chemotherapie, Immuntherapie oder adjuvante Strahlentherapie ­ Wie können wir die onkologischen Ergebnisse der radikalen Zystektomie verbessern?

According to current guidelines, patients with muscle-invasive urothelial carcinoma (pT2-pt4a pN0) should be offered neoadjuvant cisplatin-containing chemotherapy before radical cystectomy. If not used neoadjuvantly, chemotherapy can be administered in the adjuvant setting (for > pT3 or pN+ disease). Both neoadjuvant and adjuvant therapy lead to improved overall survival. In the adjuvant setting, the checkpoint inhibitor nivolumab has also been approved for treatment of PD-L1-positive tumors (tumor proportion score [TPS] ≥ 1%). On the one hand, real-world evidence shows that cisplatin-fit patients often do not receive chemotherapy and, on the other hand, that a relevant proportion of patients are also not suitable for cisplatin-based chemotherapy. Further multimodal therapeutic strategies are hence urgently needed to improve the prognosis of affected patients. In particular, the use of antibody-drug conjugates and combination strategies involving checkpoint inhibitors are currently being intensively researched.

Role of Proton Beam Therapy in Spinal Chordomas: A Narrative Review of The Literature.

Chordomas are rare malignant neoplasms arising from vestigial remnants of the embryonic notochord. Approximately 55-70% of chordomas develop within the vertebral column. Their affinity to develop within the bones of the axial skeleton and propensity to locally invade and recur makes them challenging candidates for complete surgical excision. Adjuvant therapies are hence necessary to improve outcomes; for which chemotherapy has been observed to be largely ineffective, owing to the tumour being resistant to it. Radiotherapy is the current adjuvant therapy of choice for chordoma management. Over the years, proton beam therapy (PBT) has been the subject of medical attention, given the dosimetric benefits it confers over traditional radiotherapy, allowing more concentrated radiation to be given to the target of interest and reducing damage to surrounding normal tissue. A review of the current literature reveals PBT offers significantly better outcomes when used as an adjuvant to maximal surgical resection rather than as a definitive therapy.

Investigating the Efficacy and Safety of a Dose-Dense Paclitaxel, Cyclophosphamide With Trastuzumab in Stage I-II Human Epidermal Growth Factor Receptor 2 (HER2) Positive Breast Cancer.

BACKGROUND: The evolution of systemic therapies has improved outcomes for patients with human epidermal growth factor receptor 2 positive (HER2+) breast cancer. Nonetheless, the tolerability and safety profile of systemic therapies represent an area for further improvement. Here we report the results of a phase 2 trial evaluating a nonanthracycline, nonplatinum adjuvant treatment regimen for patients following initial surgical resection. METHODS: We enrolled patients with stage I or II HER2+ breast cancer who underwent upfront surgery to receive adjuvant treatment with 6 cycles of dose-dense Paclitaxel, cyclophosphamide and Trastuzumab (PC-H) every 2 weeks, followed by 13 cycles of maintenance trastuzumab every 3 weeks to complete 52 weeks of treatment (compromising 19 cycles). The primary objective was to determine the safety and feasibility of adjuvant PC-H, measured by the completion rate frequency and the grade of adverse events, using National Cancer Institute Common Terminology Criteria. The secondary objective was to estimate relapse-free survival and overall survival. RESULTS: Between 2010 and 2019, a total of 39 patients were enrolled. Of those, 34 patients (87.18%) completed the planned treatment. Severe adverse events of grade 3 or 4 occurred in 27 patients (69.23%), including 3 patients (7.69%) with grade 3-4 decrease in ejection fraction. At median follow up of 5.6 years, all 39 patients were alive. The 5-year relapse-free survival was 94.30% (95% CI: 75.3-100). CONCLUSIONS: PC-H demonstrated overall safety and efficacy, yielding high rates of relapse-free survival among patients with early stage (HER2+) breast cancer.

Is multidisciplinary treatment effective for invasive intraductal papillary mucinous carcinoma?

Background: Surgical resection is standard treatment for invasive intraductal papillary mucinous carcinoma (IPMC); however, impact of multidisciplinary treatment on survival including postoperative adjuvant therapy (AT), neoadjuvant therapy (NAT), and treatment for recurrent lesions is unclear. We investigated the effectiveness of multidisciplinary treatment in prolonging survival of patients with invasive IPMC. Methods: This retrospective multi-institutional study included 1183 patients with invasive IPMC undergoing surgery at 40 academic institutions. We analyzed the effects of AT, NAT, and treatment for recurrence on survival of patients with invasive IPMC. Results: Completion of the planned postoperative AT for 6 months improved the overall survival (OS), disease-specific survival (DSS), and recurrence-free survival (RFS) of patients with stage IIB and stage III resected invasive IPMC, elevated preoperative carbohydrate antigen 19-9 level, lymphovascular invasion, perineural invasion, serosal invasion, and lymph node metastasis on un-matched and matched analyses. Of the patients with borderline resectable (BR) invasive IPMC, the OS (p = 0.001), DSS (p = 0.001), and RFS (p = 0.001) of patients undergoing NAT was longer than that of those without on the matched analysis. Of the 484 invasive IPMC patients (40.9%) who developed recurrence after surgery, the OS of 365 patients who received any treatment for recurrence was longer than that of those without treatment (40.6 vs. 22.4 months, p < 0.001). Conclusion: Postoperative AT might benefit selected patients with invasive IPMC, especially those at high risk of poor survival. NAT might improve the survivability of BR invasive IPMC. Any treatment for recurrence after surgery for invasive IPMC might improve survival.

Real-world effectiveness of adjuvant octreotide therapy in patients with pancreatic neuroendocrine tumors at high recurrence risk: A multicenter retrospective cohort study.

Adjuvant therapy for pancreatic neuroendocrine tumors (PanNETs) after radical resection lacks evidence-based data and remains controversial. This study aimed to validate whether long-acting octreotide is a potential candidate for adjuvant therapy in patients with G2 PanNETs at high recurrence risk by clustering real-world data. A retrospective review of patients with nonmetastatic grade 2 PanNETs who underwent radical resection at six research centers between 2008 and 2020 was conducted. Propensity score matching and inverse probability of treatment weight analysis were used to control confounding factors. Overall, 357 patients (octreotide group, n = 82; control group, n = 275) were analyzed. Kaplan-Meier survival analyses showed that the octreotide group had longer disease-free survival (DFS) compared with the control group (36 months: 93.3% vs. 79.0%, p = .0124; 60 months: 71% vs. 67.6%, p = .0596, respectively), as well as overall survival (OS) (60 months: 98% vs. 83.8%, p = .0117, respectively). Multivariate analyses indicated that octreotide long-acting repeatable (LAR) adjuvant therapy was associated with higher OS (p = .0270) at 60 months. Propensity score matching analysis showed that octreotide adjuvant therapy was associated with higher DFS (p = .0455) and OS (p = .0190) at 60 months. Similar results were obtained via inverse probability of treatment weight analysis. Subgroup analysis indicated that octreotide LAR was associated with a high DFS in patients with lymph node metastasis or Ki-67 <10% PanNETs. Adjuvant therapy with long-acting octreotide following radical resection of nonmetastatic G2 PanNETs may be associated with improved DFS and OS in a real-world setting.