HER2-targeted therapies for HER2-positive early-stage breast cancer: present and future.

Breast cancer (BC) has the second highest incidence among cancers and is the leading cause of death among women worldwide. The human epidermal growth factor receptor 2 (HER2) is overexpressed in approximately 20%-30% of BC patients. The development of HER2-targeted drugs, including monoclonal antibodies (mAbs), tyrosine kinase inhibitors (TKIs) and antibody-drug conjugates (ADCs), has improved the operation rate and pathological remission rate and reduced the risk of postoperative recurrence for HER2-positive early-stage BC (HER2+ EBC) patients. This review systematically summarizes the mechanisms, resistance, therapeutic modalities and safety of HER2-targeted drugs and helps us further understand these drugs and their use in clinical practice for patients with HER2+ EBC.

Role of Adjuvant Chemotherapy After Curative Resection in Stage II and III Rectal Cancer.

INTRODUCTION: Patients with resected locally advanced rectal cancer (LARC) and an incomplete total mesorectal excision (TME) have worse oncologic outcomes. The associations between TME grade, adjuvant therapy receipt, and oncologic outcomes have not been well-studied. We aimed to determine the association between adjuvant chemotherapy and oncologic outcomes in patients who underwent neoadjuvant chemoradiation (CRT) or short-course radiotherapy (SCRT) followed by proctectomy and to evaluate this association stratified by TME grade. MATERIALS AND METHODS: We analyzed a retrospective multi-institutional cohort of primary LARC patients diagnosed between 2010 and 2018 who received neoadjuvant CRT/SCRT followed by proctectomy. Complete TME was defined as complete mesorectal excision, and noncomplete TME was defined as near-complete or incomplete TME. We used adjusted Cox proportional hazards regression to test the association between adjuvant chemotherapy and mortality or locoregional recurrence (LRR) across groups. RESULTS: We identified 746 eligible patients. On final pathology, 101 (13.5%) had noncomplete and 645 (86.5%) had complete TME. Rates of adjuvant chemotherapy receipt were similar between noncomplete and complete TME groups (70.3% and 69.5%, respectively). Mean follow-up interval was 35 mo. Adjuvant chemotherapy was associated with lower risk of mortality (HR 0.27, 95% CI 0.19-0.39, P < 0.001); the same association existed when stratifying patients by TME grade. For patients with a complete TME, adjuvant chemotherapy was associated with lower LRR (HR 0.08, 95% CI 0.01-0.56, P = 0.01). The LRR model for the noncomplete TME group did not converge due to few captured recurrences. CONCLUSIONS: These data show an association between adjuvant chemotherapy and positive outcomes in LARC patients receiving neoadjuvant CRT/SCRT followed by proctectomy.

An open label, single-centric, post market clinical study to evaluate the safety and efficacy of a new antimicrobial wound dressing (VELVERT) as an adjuvant therapy in the treatment of venous leg ulcer.

OBJECTIVES: An open label, single-centric, post market clinical study was undertaken to evaluate the safety and efficacy of a new antimicrobial wound dressing (VELVERT) as an adjuvant therapy in the treatment of venous leg ulcer (VLU). METHODS: Patients with VLU of grade C-5 according to CEAP classification and above were evaluated using doppler ultra sound. The efficacy of new antimicrobial wound dressing (VELVERT) was assessed in terms of wound area reduction within a time frame of 60 days and surgeon questioners. Patients were evaluated for VELVERT safety and pain level on a scale of 0-10 Numeric Pain Chart. Presence of micro-organism load was monitored at regular time interval. RESULTS: VELVERT treatment was effective as 71.43% reduction in the ulcer area was observed. After 60 days, a total of 9 (45%) patients had complete ulcer closure. A remarkable decrease in the severity of pain was observed with 11 (55%) patients expressing no pain at the EOT. Swab test showed negative result for micro-organism growth. No serious adverse events were observed during the trial. CONCLUSION: The data indicates that VELVERT is an effective treatment for VLUs and showed the potential in the wound care of VLUs.

Polycystic ovary syndrome and type 1 diabetes - the current state of knowledge.

Type 1 diabetes mellitus (T1DM) is characterized by an increased prevalence of polycystic ovary syndrome (PCOS) with its negative metabolic consequences, including increased cardiovascular risk. Both diseases affect patients, significantly deteriorating the quality of life. During the treatment of patients with T1DM and PCOS, lifestyle modification and increased physical activity resulting in weight reduction should always be recommended. Pharmacological treatment should be applied in accordance with the current standards. In most of these patients metformin alone or with combined oral contraceptive pills could be considered for cycle regulation. In obese patients with T1DM and PCOS glucagon-like peptide-1 receptor agonists (GLP-1 Ras) (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptides (GIP)/GLP-1 RAs (tirzepatide) are regarded as a safe approach. Anti-androgens could also be considered especially to treat hirsutism and hyperandrogenism in women with PCOS. There are relatively limited evidence on anti-androgens in PCOS and we should consider use them in only selected cases. Some other substances may have a positive effect on patients with T1DM and PCOS include inositol, alpha-lipoic acid, folic acid, vitamins (B1, B6, B12, D, K, E, A), chromium and selenium compounds, as well as omega-3 fatty acids. The gut microbiome is also considered as a critical modulator of the predisposition to PCOS and T1DM and may be the future goal of the treatment. The proper treatment of PCOS will translate into a reduction in the severity of typical symptoms and also into the improvement in the metabolic control of diabetes and the patients' quality of life.

Missed Adjuvant Therapy in Human Papillomavirus Positive Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVE: Investigate missed adjuvant therapy and associated disparities in overall survival (OS) for human papillomavirus-associated (HPV+) oropharyngeal squamous cell carcinoma (OPSCC). METHODS: The 2010-2017 National Cancer Database was queried for patients with surgically resected HPV+ OPSCC. Indications for adjuvant radiotherapy (aRT) included pT3-4 classification, pN2-3 classification, lymphovascular invasion, pathologic extranodal extension (pENE), and/or positive surgical margins (PSM). Indication(s) for adjuvant chemoradiotherapy (aCRT) included pENE and/or PSM. Multivariable logistic and Cox regression models were implemented. RESULTS: Of 5297 patients satisfying inclusion criteria, 4288 had indication(s) for aRT; 775 did not receive any adjuvant therapy and were considered as missing aRT. A total of 2234 patients had indication(s) for aCRT. Of these, 1383 (61.9%) received aCRT, 555 (24.8%) patients received aRT alone and were considered as having missed aCRT, and 296 (13.2%) did not receive any adjuvant therapy. Missed aRT and missed aCRT were each associated with age, treatment facility type, pN classification, and surgical margin status (p < 0.015). Among patients with indication(s) for aRT alone, OS of those receiving no adjuvant therapy, aRT alone, and aCRT was 90.0%, 94.8%, and 93.4%, respectively (p = 0.080). Among patients with indication(s) for aCRT, those receiving aRT alone and aCRT had similar OS (89.0% vs. 86.6%, p = 0.357) which was superior to receiving no adjuvant therapy (74.9%, p < 0.001). These patterns in OS persisted on multivariable Cox regression. CONCLUSION: Among patients with HPV+ OPSCC and indication(s) for aRT, missed aRT was not associated with worse OS. For patients with indication(s) for aCRT, aRT alone was associated with similar OS as aCRT. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

A multicenter retrospective study on neck dissection and adjuvant radiotherapy with transoral surgery for hypopharyngeal squamous cell carcinoma.

OBJECTIVE: The aim of this multicenter retrospective study was to analyze the impact of prophylactic neck dissection and adjuvant therapy in transoral surgery for hypopharyngeal cancer. METHODS: We compared the impact of surgical margin assessment, neck dissection, and adjuvant treatment on oncologic outcomes in patients who underwent transoral surgery for hypopharyngeal squamous cell carcinoma between 2015 and 2021. RESULTS: Two hundred and twenty-one patients were included. The 3-year local recurrence-free survival was 89.1 %, and local recurrence did not significantly impact overall survival. Positive vertical margins resulted in 60 % of patients receiving additional treatment, with no increase in local recurrence and a significant increase in regional recurrence (p = 0.007) and distant metastasis (p < 0.001). Half of the patients with regional recurrence after neck dissection also had distant metastases and worse survival (p = 0.069), while those with regional recurrence without prophylactic neck dissection did not have worse survival. CONCLUSION: In cases of positive vertical margin, careful surveillance for regional recurrence and distant metastasis is also warranted. Prophylactic neck dissection may not be necessary.

Predictors of mastectomy in breast cancer patients with complete remission of primary tumor after neoadjuvant therapy: A retrospective study.

INTRODUCTION: Neoadjuvant therapy (NAT) should increase the rate of breast-conserving surgery (BCS) in non-metastatic breast cancer (BC) patients, especially in those achieving tumor shrinkage. Still, the conversion from a pre-planned mastectomy to BCS in patients responding to NAT is not a widespread standard. We aimed to identify factors influencing surgical choices in this setting. MATERIALS AND METHODS: We retrospectively collected data of BC patients with complete remission of primitive tumor (ypT0) after NAT, treated with BCS or mastectomy in two Italian breast units. Predictors of mastectomy were explored using logistic regression. Distant recurrence and event-free survival were assessed in the BCS and mastectomy cohort. RESULTS: 243 patients were included, 147 (60.5 %) treated with BCS and 96 (39.5 %) treated with mastectomy. In the mastectomy group, there were more centrally-located, multiple and larger tumors. At univariate regression analysis, central location, baseline tumor extension on ultrasound (US) and magnetic resonance imaging (MRI), multiple foci and clinical stage were significantly associated with the chance of receiving mastectomy. At multivariate analysis, only baseline focality on US and extension on MRI retained significance as predictors of mastectomy. Distant recurrence and event-free survival were significantly longer in patients undergoing BCS. CONCLUSION: Baseline tumor extension and focality were the main predictors of mastectomy in patients with ypT0 after NAT. However, BCS did not negatively affect survival outcomes in our cohort. An effort should be made to avoid potentially unnecessary mastectomy in this population, aiming at minimizing surgery-associated toxicities and improving patients' quality of life.

Research progress on prognostic factors of gallbladder carcinoma.

BACKGROUND: Gallbladder carcinoma is the most common malignant tumor of the biliary system, and has a poor overall prognosis. Poor prognosis in patients with gallbladder carcinoma is associated with the aggressive nature of the tumor, subtle clinical symptoms, ineffective adjuvant treatment, and lack of reliable biomarkers. PURPOSE: Therefore, evaluating the prognostic factors of patients with gallbladder carcinoma can help improve diagnostic and treatment methods, allowing for tailored therapies that could benefit patient survival. METHODS: This article systematically reviews the factors affecting the prognosis of gallbladder carcinoma, with the aim of evaluating prognostic risk in patients. CONCLUSION: A comprehensive and in-depth understanding of prognostic indicators affecting patient survival is helpful for assessing patient survival risk and formulating personalized treatment plans.

Acupuncture as Adjuvant Therapy for Glaucoma: Protocol for a Randomized Controlled Trial.

BACKGROUND: Glaucoma is a chronic progressive optic neuropathy that necessitates lifelong treatment to reduce the decline of the optic nerve. Due to the extended and continuous treatments required for patients, complementary therapies are often considered alongside conventional treatments to enhance the effectiveness of the treatment. Acupuncture has demonstrated the potential to lower intraocular pressure in previous clinical trials, making it a promising glaucoma intervention. OBJECTIVE: The primary objective of this study is to conduct a single-center randomized control trial involving patients with glaucoma. Acupuncture will be evaluated as an adjunctive therapy. The trial aims to explore its effectiveness for glaucoma. METHODS: In this single-center randomized controlled trial, participants (N=50) with primary open-angle glaucoma will be randomly assigned to the treatment group, receiving ophthalmic acupuncture with "De Qi" sensation, or the control group, receiving minimum acupuncture stimulation on nonophthalmic acupoints. The intervention will consist of weekly acupuncture treatments for a total of 6 sessions. Participants will be assessed at 8 time points, which are baseline, during the intervention (6 times), and at a 3-month follow-up. The primary outcome measure is a change in the intraocular pressure before and after each acupuncture treatment. Secondary outcomes will include measurements of heart rate and blood pressure before and after acupuncture, best-corrected visual acuity, visual field, optical coherence tomography, optical coherence tomography angiography, the Glaucoma Symptom Scale, and the Glaucoma Quality of Life-15 questionnaire. RESULTS: Recruitment of participants for the trial commenced on June 28, 2023. A total of 10 participants have been enrolled to test the feasibility of the experiment. We anticipate that the preliminary data from this trial will be completed by December 2025. CONCLUSIONS: This trial uses rigorous methodology and comprehensive outcome measurements to assess the clinical efficacy of acupuncture as an adjunctive therapy for glaucoma, providing valuable insights for future clinical treatment guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT05753137; https://clinicaltrials.gov/study/NCT05753137. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57888.

Does prepectoral placement delay adjuvant therapies compared to retropectoral immediate implant-based breast reconstruction? A retrospective analysis.

BACKGROUND: Prepectoral (PP) immediate implant-based breast reconstruction (IBBR) is becoming increasingly popular compared to retropectoral (RP) reconstruction. This study compares the timing of administration of different adjuvant therapy (ATs) after PP or RP IBBR. PATIENTS AND METHODS: A monocentric retrospective analysis was conducted on patients undergoing mastectomy and IBBR from January 2018 to December 2023. Preoperative characteristics, mastectomy procedure type, PP or RP implant placement, postoperative outcomes, AT type, and time between surgery and AT administration were collected and analyzed. RESULTS: 167 patients (206 breasts) were included. 123 underwent PP IBBR and 44 RP IBBR. The mean time between surgery and first AT administration was similar in the PP group (45.7 days, SD 39.3) compared to the RP group (37.4 days, SD 33.1) (p-value 0.2100). No significant differences were found in the timing of endocrine therapy (ET), chemotherapy (CT), or radiotherapy (RT) initiation between the PP and RP groups. Patients with seroma had a delayed initiation of CT (83.67 days, SD 123.7) versus those without seroma (42.1 days, SD 29.7) (p-value 0.0298). CONCLUSIONS: The average time between surgery and administration of the first AT following PP IBBR was similar compared to RP IBBR. Postoperative seromas were associated with delayed CT in the overall population.

Cost-effectiveness of pembrolizumab as an adjuvant treatment of renal cell carcinoma post-nephrectomy in Switzerland.

AIMS: Pembrolizumab has demonstrated significantly prolonged disease-free survival and overall survival (OS) among adult patients post-nephrectomy who have an intermediate-high risk, high-risk, or M1 stage with no evidence of disease (M1 NED) renal cell carcinoma (RCC) with clear cell component. The aim of this study was to evaluate the cost-effectiveness of pembrolizumab for patients with RCC post-nephrectomy versus observation in Switzerland. MATERIALS AND METHODS: A previously published Markov model was adapted for the Swiss setting to estimate the cost-effectiveness of adjuvant pembrolizumab versus observation from the Swiss statutory health insurance perspective. Transition probabilities between model states were estimated using survival curves from KEYNOTE-564 (data cut-off: June 14, 2021). Outcomes included costs (2022 Swiss francs [CHF]), quality-adjusted life-years (QALYs), and life-years (LYs), measured over a lifetime horizon. Costs included drug acquisition and administration for adjuvant and subsequent therapy. Both costs and effectiveness were discounted at 3.0% annually. Cost-effectiveness was evaluated at a hypothetical willingness-to-pay (WTP) threshold of CHF 100,000 Sensitivity was assessed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. RESULTS: Over a lifetime horizon, the total incremental cost for pembrolizumab versus observation was CHF 59,089, providing incremental gains of 0.90 QALYs (1.07 LYs); the incremental cost-effectiveness ratio was CHF 65,299/QALY. Pembrolizumab was deemed cost-effective versus observation, with a 69.9% probability of cost-effectiveness. LIMITATIONS: A more recent interim analysis data cut from KEYNOTE-564 with median follow up of 57.2 months has since been published; however, these were not available at the time of analysis. It would likely have minimal impact on transition probabilities from disease-free, and the current approach remains conservative for predicting OS for pembrolizumab. CONCLUSIONS: As an adjuvant treatment of RCC post-nephrectomy, pembrolizumab was found to be cost-effective versus observation in Switzerland at a WTP threshold of CHF 100,000/QALY. Policy makers should consider pembrolizumab as an adjuvant treatment for patients with RCC post-nephrectomy when making decisions regarding resource allocation.

Updates in Systemic Treatment of Hormone Receptor-Positive Early-Stage Breast Cancer.

OPINION STATEMENT: Hormone-receptor positive (HR +) and human epidermal growth factor receptor 2 (HER2) negative early breast cancer (eBC) is a heterogeneous disease with several contributing factors for increased risk of recurrence, including tumor features, individual biomarkers, and genomic risk. The current standard approach in the management of HR + /HER2neg eBC includes chemotherapy and endocrine therapy (ET), and additional therapies based on risk profile, menopausal status, and genetics are sometimes appropriate. The risk of recurrence is more pronounced in patients with high-risk eBC including large tumor size, nodal involvement, high proliferative index, and genetic predisposition. In premenopausal patients with high-risk eBC, ovarian function suppression in combination with adjuvant ET improves survival. In postmenopausal patients, extended aromatase inhibitor (AI) therapy can be considered. Recent trials have identified novel treatment approaches to reduce the risk of recurrence in high-risk HR + /HER2neg eBC including the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to adjuvant ET. For patients with germline BRCA1/BRCA2 mutations, adjuvant poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors have been shown to improve overall survival (OS). However, despite these recent advances, the risk of recurrence remains substantial, highlighting an area of unmet need. There are several ongoing clinical trials further investigating the role of CDK 4/6 inhibitors and immunotherapy in high-risk HR + /HER2neg eBC.

Current National Treatment Trends for Gastric Adenocarcinoma in the United States.

PURPOSE: The treatment of gastric adenocarcinoma (GA) continues to evolve. While neoadjuvant chemotherapy (NAC) has demonstrated emerging benefit, the optimal treatment regimen, and sequence remain to be firmly established. METHODS: Patients with nonmetastatic GA who underwent resection were identified within the 2020 National Cancer Database. Patients were compared between the mutually exclusive treatment groups of NAC, neoadjuvant chemoradiotherapy (NCRT), adjuvant chemotherapy, adjuvant chemoradiotherapy (CRT), and surgery only. The primary endpoint was receipt of NAC or NCRT. Patients were 1-to-1 propensity score matched for receiving any neoadjuvant therapy. Multivariable logistic regression was used to identify predictors of receipt of any neoadjuvant therapy and receipt of any adjuvant therapy. RESULTS: Twenty-five thousand and seventy-three patients were included in the analysis. Patients were treated with NAC (25.0%), NCRT (31.4%), adjuvant chemotherapy (6.5%), adjuvant CRT (12.6%), and surgery only (24.5%). Compared to 2006-2011, patients diagnosed between 2012 and 2017 experienced the greatest increases in NAC (18.6% vs. 29.0%; p < 0.001) and NCRT (25.0% vs. 35.5%; p < 0.001). Median OS was 44.9 months. OS was longest for patients who received any neoadjuvant therapy compared to those receiving adjuvant or surgery only (51.0 vs. 42.4 vs. 38.0 months, respectively; p < 0.001). Patients who were Black, in the lowest income quartile or treated at lower volume facilities were less likely to receive NAT (all p < 0.001). CONCLUSIONS: There has been significant acceleration in the use of neoadjuvant therapy for GA. Currently, NCRT followed by surgery are the most common treatment sequences in the United States. Additional trials are needed to further define the optimal treatment sequence.

Safety and efficacy of fecal microbiota transplantation (FMT) as a modern adjuvant therapy in various diseases and disorders: a comprehensive literature review.

The human gastrointestinal (GI) tract microbiome is a complex and all-encompassing ecological system of trillions of microorganisms. It plays a vital role in digestion, disease prevention, and overall health. When this delicate balance is disrupted, it can lead to various health issues. Fecal microbiota transplantation (FMT) is an emerging therapeutic intervention used as an adjuvant therapy for many diseases, particularly those with dysbiosis as their underlying cause. Its goal is to restore this balance by transferring fecal material from healthy donors to the recipients. FMT has an impressive reported cure rate between 80% and 90% and has become a favored treatment for many diseases. While FMT may have generally mild to moderate transient adverse effects, rare severe complications underscore the importance of rigorous donor screening and standardized administration. FMT has enormous potential as a practical therapeutic approach; however, additional research is required to further determine its potential for clinical utilization, as well as its safety and efficiency in different patient populations. This comprehensive literature review offers increased confidence in the safety and effectiveness of FMT for several diseases affecting the intestines and other systems, including diabetes, obesity, inflammatory and autoimmune illness, and other conditions.

Management of Patients with Advanced Prostate Cancer. Report from the 2024 Advanced Prostate Cancer Consensus Conference (APCCC).

BACKGROUND AND OBJECTIVE: Innovations have improved outcomes in advanced prostate cancer (PC). Nonetheless, we continue to lack high-level evidence on a variety of topics that greatly impact daily practice. The 2024 Advanced Prostate Cancer Consensus Conference (APCCC) surveyed experts on key questions in clinical management in order to supplement evidence-based guidelines. Here we present voting results for questions from APCCC 2024. METHODS: Before the conference, a panel of 120 international PC experts used a modified Delphi process to develop 183 multiple-choice consensus questions on eight different topics. Before the conference, these questions were administered via a web-based survey to the voting panel members ("panellists"). KEY FINDINGS AND LIMITATIONS: Consensus was a priori defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. The voting results show varying degrees of consensus, as discussed in this article and detailed in the Supplementary material. These findings do not include a formal literature review or meta-analysis. CONCLUSIONS AND CLINICAL IMPLICATIONS: The voting results can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers in prioritising areas for future research. Diagnostic and treatment decisions should always be individualised on the basis of patient and cancer characteristics, and should incorporate current and emerging clinical evidence, guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2024 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials.

The efficacy of adjuvant mitotane therapy and radiotherapy following adrenalectomy in patients with adrenocortical carcinoma: A systematic review and meta-analysis.

Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a high recurrence rate after surgical therapy with curative intent. Adjuvant radiotherapy (RT) and mitotane therapy have been proposed as options following the adrenalectomy. However, the efficacy of adjuvant RT or mitotane therapy remains controversial. We aimed to evaluate the efficacy of adjuvant therapy in patients who underwent adrenalectomy for localised ACC. The PubMed, Scopus, and Web of Science databases were queried on March 2024 for studies evaluating adjuvant therapies in patients treated with surgery for localized ACC (PROSPERO: CRD42024512849). The endpoints of interest were overall survival (OS) and recurrence-free survival (RFS). Hazard ratios (HR) with 95% confidence intervals (95%CI) were pooled in a random-effects model meta-analysis. One randomized controlled trial (n = 91) and eleven retrospective studies (n = 4,515) were included. Adjuvant mitotane therapy was associated with improved RFS (HR: 0.63, 95%CI: 0.44-0.92, p = 0.016), while adjuvant RT did not reach conventional levels of statistical significance (HR:0.79, 95%CI:0.58-1.06, p = 0.11). Conversely, Adjuvant RT was associated with improved OS (HR:0.69, 95%CI:0.58-0.83, p<0.001), whereas adjuvant mitotane did not (HR: 0.76, 95%CI: 0.57-1.02, p = 0.07). In the subgroup analyses, adjuvant mitotane was associated with better OS (HR:0.46, 95%CI: 0.30-0.69, p < 0.001) and RFS (HR:0.56, 95%CI: 0.32-0.98, p = 0.04) in patients with negative surgical margin. Both adjuvant RT and mitotane were found to be associated with improved oncologic outcomes in patients treated with adrenalectomy for localised ACC. While adjuvant RT significantly improved OS in general population, mitotane appears as an especially promising treatment option in patients with negative surgical margin. These data can support the shared decision-making process, better understanding of the risks, benefits, and effectiveness of these therapies is still needed to guide tailored management of each individual patient.

Impact of Gene Expression Classifier Testing on Adjuvant Treatment Following Radical Prostatectomy: The G-MINOR Prospective Randomized Cluster-crossover Trial.

BACKGROUND AND OBJECTIVE: Decipher is a tissue-based genomic classifier (GC) developed and validated in the post-radical prostatectomy (RP) setting as a predictor of metastasis. We conducted a prospective randomized controlled cluster-crossover trial assessing the use of Decipher to determine its impact on adjuvant treatment after RP. METHODS: Eligible patients had undergone RP within 9 mo of enrollment, had pT3-4 disease and/or positive surgical margins, and prostate-specific antigen <0.1 ng/ml. Centers were randomized to a sequence of 3-mo periods of either GC-informed care or usual care (UC). Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) recurrence risk scores were provided to treating physicians and patients in all periods. KEY FINDINGS AND LIMITATIONS: Impact of GC test results on adjuvant treatment were compared with UC alone. Longitudinal patient-reported urinary and sexual function was assessed. A total of 175 patients were enrolled in 27 periods with GC and 163 in 28 periods with UC. At 18 mo after RP, an average patient in the GC arm received adjuvant treatment 9.7% of the time compared with 8.7% for an average individual in the UC arm (0.99% mean difference, 95% confidence interval [CI] -7.6%, 9.6%, p = 0.8). While controlling for CAPRA-S score, higher GC scores tended to result in an increased likelihood of adjuvant treatment that was not statistically significant (odds ratio [OR] = 1.35 per 0.1 increase in GC score, 95% CI 0.98-1.85, p = 0.066). Using the GC risk groups, reflecting clinical use, a high GC risk was associated with significantly higher odds of receiving adjuvant treatment (OR = 6.9, 95% CI 1.8, 26, p = 0.005) compared with a low GC score, adjusted for CAPRA-S score. There were no differences in patient-reported urinary and sexual function between the study arms. As oncologic outcomes are immature, the present data cannot address whether GC testing provides any cancer control benefit. CONCLUSIONS AND CLINICAL IMPLICATIONS: GC testing impacts adjuvant therapy administration when viewed through the risk categories presented in the patient report; however, these data do not provide specific support for GC testing in the adjuvant treatment setting.

Therapeutic efficacies of remnant ablation and radioiodine adjuvant therapy in differentiated thyroid cancer.

BACKGROUND: Successful ablation in 131I therapy for differentiated thyroid cancer (DTC) includes both remnant ablation (RA) and radioiodine adjuvant therapy (RAT). This study aimed to differentiate between the therapeutic efficacies of RA and RAT, investigate the factors associated with their effectiveness, and assess their impact on prognosis. METHODS: This retrospective study included patients with DTC who underwent initial 131I therapy at our tertiary center. The successful RA (SRA) and successful RAT (SRAT) was determined based on the 131I-diagnostic whole-body scan (Dx-WBS), TSH-stimulated thyroglobulin (sTg) levels, and neck ultrasound at the 6th month after 131I therapy. The patients were divided into complete response and persistent/recurrent disease groups during the follow-up period. RESULTS: A total of 232 patients were included, 91.8% (213/232) of patients achieved SRA, only 8.1% (19/232) failed RA (FRA). Among the 213 patients in the SRA group, 70.4% (150/213) achieved SRAT and 29.6% (63/213) failed RAT (FRAT). Only pre-ablation sTg >10 ng/mL (OR = 46.968, 95% CI 9.731-226.699, P < 0.001) was an independent risk factor predicting the failure of RAT. The prognostic analysis included 215 patients, and 6.1% (13/215) were classified as persistent/recurrent disease at the last follow-up. Both pre-ablation sTg >10 ng/mL (HR = 4.765, 95% CI 1.371-16.566, P = 0.014) and FRAT (HR = 10.104, 95% CI 1.071-95.304, P = 0.043) independently predicted persistent/recurrent disease. CONCLUSIONS: RA is easy to achieve successfully, whereas RAT evaluation provides greater value than RA for prognosis prediction. For patients with low Tg levels and no imaging evidence of disease, routine Dx-WBS during follow-up has minimal significance.

Impact of Duration of Adjuvant Therapy on Patients with Initially Unresectable Hepatocellular Carcinoma After Conversion Surgery: A Propensity Score Matching Study.

Background: This study aimed to assess the effect of adjuvant therapy with different durations in patients with initially unresectable hepatocellular carcinoma (uHCC) after conversion surgery. Methods: This study included 85 patients with initially uHCC who received conversion surgery between May 2019 and November 2022. They were divided into the long duration group (n = 57) and short duration group (n = 28) based on postoperative medication duration. Recurrence-free survival (RFS) and overall survival (OS) were analyzed and compared between the cohorts. Results: No significant difference in RFS or OS was found between the two groups [RFS: hazard ratio (HR) = 0.486; 95% confidence interval (CI), 0.229-1.034, P = 0.061; OS: HR = 0.377; 95% CI, 0.119-1.196, P = 0.098]. Patients without major pathologic response (MPR) in the long duration group had better RFS and OS results compared to those in the short duration group (RFS: HR = 0.242; 95% CI, 0.092-0.634, P = 0.004; OS: HR = 0.264; 95% CI, 0.079-0.882, P = 0.031). No significant difference was detected in RFS or OS between the two groups in patients with MPR (RFS: HR = 1.250; 95% CI, 0.373-4.183, P = 0.718; OS: HR = 7.389; 95% CI, 0.147-372.4, P = 0.317). After propensity score matching, 25 pairs of patients were selected and the results remained consistent. Conclusion: At least 6 months of adjuvant therapy may be beneficial for patients without MPR after conversion surgery. However, in patients with MPR, the effect of adjuvant therapy remains unclear. Further studies are needed to confirm the optimal duration of adjuvant therapy.

Adjuvant Therapy in Acral Melanoma: A Systematic Review.

Background: Acral melanoma presents distinct biological characteristics compared to cutaneous melanoma. While adjuvant therapeutic strategies for high-risk resected acral melanoma closely resemble those for cutaneous melanoma, the evidence supporting the clinical application of adjuvant therapy for acral melanoma remains inadequate. Our aim was to systematically analyze the efficacy and safety profile of adjuvant therapy in acral melanoma. Methods: This systematic review adhered to a pre-registered protocol. We comprehensively searched four electronic databases and reference lists of included articles to identify eligible studies. The primary outcome was therapeutic efficacy, and the secondary outcome was adverse events (AEs). Results: This systematic review included 11 studies with 758 acral melanoma patients undergoing adjuvant therapy. High-dose interferon α-2b (IFN) regimens showed no significant difference in recurrence-free survival (RFS), though the longer regimen was linked to increased hepatotoxicity. Adjuvant anti-PD-1 therapy demonstrated varying efficacy, with improved RFS in patients who experienced immune-related AEs. Targeted therapy with dabrafenib plus trametinib achieved high 12-month RFS in patients with BRAF-mutated acral melanoma. Comparative studies suggested that adjuvant anti-PD-1 therapy is similarly effective to IFN in prolonging survival for high-risk acral melanoma patients. Additionally, prior treatment with pegylated IFN enhanced RFS in patients receiving adjuvant pembrolizumab. Conclusion: High-dose IFN was widely used as adjuvant therapy for acral melanoma, but serious AEs prompted the search for alternatives. Adjuvant anti-PD-1 therapy shows promise, though it may be less effective than in non-acral melanoma. Further prospective studies are needed to determine the optimal adjuvant treatment for acral melanoma.