The safety and efficacy of Compound Kushen Injection with chemoradiotherapy for the outcomes of lung and gastrointestinal cancers: A PRIMSA-compliant meta-analysis.

BACKGROUND: Compound Kushen injection (CKI) is a mixture of natural compounds extracted from Radix Sophorae and Smilax glabra Roxb. CKI, as an antitumor preparation, plays a vital role in the clinical treatment of lung and gastrointestinal cancers. METHODS: Electronic databases such as the China National Knowledge Infrastructure, Wanfang data, PubMed, EMBASE, and Web of Science were searched for studies. The included studies were evaluated according to the Cochrane Handbook for Systematic Reviews, and meta-analyses were performed using RevMan 5.3 software. RESULTS: Twenty-four randomized controlled trials were selected for meta-analysis. The outcomes showed that CKI adjuvant therapy significantly improved complete remission (CR) and partial response (PR) compared to patients without CKI treatment in gastrointestinal cancers (CR: odds ratio [OR] = 1.76, 95% confidence interval [CI]: [1.29, 2.41], P = .0004; PR: OR = 1.64, 95% CI: [1.29, 2.07], P =.0001), and lung cancer (CR: OR = 2.18, 95% CI: [1.36, 3.51], P = .001); PR: OR = 1.81, 95% CI: [1.31, 2.50], P = .0003). CKI adjuvant therapy had a statistically significant advantage in optimizing life and health status (quality of life [QOL] for gastrointestinal cancers: MD = 1.76, 95% CI: [6.41, 13.80], P = .001, and Karnofsky performance status [KPS] for gastrointestinal cancers: MD = 4.64, 95% CI: [2.72, 6.57], P = .001; KPS for lung cancer: MD = 6.24, 95% CI [1.78, 10.71], P = .006). CKI reduced the pain in lung cancer patients (MD = -1.76, 95% CI: [-1.94, -1.58], P < .00001), increased immunity level (MD = 2.51, 95% CI: [2.17, 2.85], P < .00001), and alleviated the adverse reactions for lung and gastrointestinal cancers (MD = 0.38, 95% CI: (0.32, 0.46); P < .00001). CONCLUSION: The combination of CKI and chemoradiotherapy for treating lung and gastrointestinal cancer has positive effects on short-term and long-term outcomes and has advantages over chemoradiotherapy alone regarding safety and efficacy.

Interdisciplinary Spanish consensus on a watch-and-wait approach for rectal cancer / Consenso español interdisciplinar sobre un enfoque de vigilancia y espera en el cáncer de recto

Watch-and-wait has emerged as a new strategy for the management of rectal cancer when a complete clinical response is achieved after neoadjuvant therapy. In an attempt to standardize this new clinical approach, initiated by the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), and with the participation of the Spanish Association of Coloproctology (AECP), the Spanish Society of Pathology (SEAP), the Spanish Society of Gastrointestinal Endoscopy (SEED), the Spanish Society of Radiation Oncology (SEOR), and the Spanish Society of Medical Radiology (SERAM), we present herein a consensus on a watch-and-wait approach for the management of rectal cancer. We have focused on patient selection, the treatment schemes evaluated, the optimal timing for evaluating the clinical complete response, the oncologic outcomes after the implementation of this strategy, and a protocol for surveillance of these patients.(AU)

Postoperative chemoradiotherapy in patients with locally advanced gastric cancer with poor pathologic response to neoadjuvant chemotherapy.

PURPOSE: To evaluate the effect of postoperative chemoradiotherapy (CRT) in patients with locally advanced gastric cancer (LAGC) who respond poorly to neoadjuvant chemotherapy (ChT). MATERIALS AND METHODS: The database of a tertiary medical center (2009-2020) was retrospectively reviewed for patients with LAGC in whom the initial treatment strategy consisted of perioperative ChT and surgery. Those who were subsequently referred for postoperative CRT because of a poor pathologic primary-tumor response (ypT3-4, ypN2-3, R1 resection) were selected for the study. CRT consisted of 45 Gy in 25 fractions of 1.8 Gy combined with capecitabine 825 mg/m2 twice daily on radiotherapy days or continuous infusion of 5-fluorouracil 180 mg/m2/day. RESULTS: The cohort included 26 patients of median age 61 years with LAGC (clinical stage IIA-III) after surgery with D1-D2 lymphadenectomy. R0 resection was achieved in 15 (58%). The pathological stage was III in 69% (IIA-IVA). Treatment was well tolerated. During a median follow-up time of 39 months, recurrences were documented in 14 patients (54%): 11 distant and 3 locoregional. Median progression-free survival was 23 months, and median overall survival was 65 months. Estimated 5-year survival rates were 42 and 54%, respectively. CONCLUSIONS: This small retrospective study suggests that in patients with LAGC who show a poor pathologic response to neoadjuvant ChT, a good outcome relative to reference arms in randomized trials can still be achieved with the addition of postoperative CRT. Further studies of the benefit of a tailored adaptive treatment approach to LAGC based on the response to neoadjuvant ChT are warranted.

Dyadic Yoga for Head and Neck Cancer Patients Undergoing Chemoradiation and their Family Caregivers.

OBJECTIVES: Concurrent chemoradiation to treat head and neck cancer (HNC) may result in debilitating toxicities. Targeted exercise such as yoga therapy may buffer against treatment-related sequelae; thus, this pilot RCT examined the feasibility and preliminary efficacy of a yoga intervention. Because family caregivers report low caregiving efficacy and elevated levels of distress, we included them in this trial as active study participants. METHODS: HNC patients and their caregivers were randomized to a 15-session dyadic yoga program or a waitlist control (WLC) group. Prior to randomization, patients completed standard symptom (MDASI-HN) and patients and caregivers completed quality of life (SF-36) assessments. The 15-session program was delivered parallel to patients' treatment schedules. Participants were re-assessed at patients' last day of chemoradiation and again 30 days later. Patients' emergency department visits, unplanned hospital admissions and gastric feeding tube placements were recorded over the treatment course and up to 30 days later. RESULTS: With a consent rate of 76%, 37 dyads were randomized. Participants in the yoga group completed a mean of 12.5 sessions and rated the program as "beneficial." Patients in the yoga group had clinically significantly less symptom interference and HNC symptom severity and better QOL than those in the WLC group. They were also less likely to have a hospital admission (OR = 3.00), emergency department visit (OR = 2.14), and/or a feeding tube placement (OR = 1.78). CONCLUSION: Yoga therapy appears to be a feasible, acceptable, and possibly efficacious behavioral supportive care strategy for HNC patients undergoing chemoradiation. A larger efficacy trial is warranted.

Practice Patterns for Organ Preservation in US Patients With Rectal Cancer, 2006-2020.

Importance: In March 2023, the National Comprehensive Cancer Network endorsed watch and wait for those with complete clinical response to total neoadjuvant therapy. Neoadjuvant therapy is highly efficacious, so this recommendation may have broad implications, but the current trends in organ preservation in the US are unknown. Objective: To describe organ preservation trends among patients with rectal cancer in the US from 2006 to 2020. Design, Setting, and Participants: This retrospective, observational case series included adults (aged ≥18 years) with rectal adenocarcinoma managed with curative intent from 2006 to 2020 in the National Cancer Database. Exposure: The year of treatment was the primary exposure. The type of therapy was chemotherapy, radiation, or surgery (proctectomy, transanal local excision, no tumor resection). The timing of therapy was classified as neoadjuvant or adjuvant. Main Outcomes and Measures: The primary outcome was the absolute annual proportion of organ preservation after radical treatment, defined as chemotherapy and/or radiation without tumor resection, proctectomy, or transanal local excision. A secondary analysis examined complete pathologic responses among eligible patients. Results: Of the 175 545 patients included, the mean (SD) age was 63 (13) years, 39.7% were female, 17.4% had clinical stage I disease, 24.7% had stage IIA to IIC disease, 32.1% had stage IIIA to IIIC disease, and 25.7% had unknown stage. The absolute annual proportion of organ preservation increased by 9.8 percentage points (from 18.4% in 2006 to 28.2% in 2020; P < .001). From 2006 to 2020, the absolute rate of organ preservation increased by 13.0 percentage points for patients with stage IIA to IIC disease (19.5% to 32.5%), 12.9 percentage points for patients with stage IIIA to IIC disease (16.2% to 29.1%), and 10.1 percentage points for unknown stages (16.5% to 26.6%; all P < .001). Conversely, patients with stage I disease experienced a 6.1-percentage point absolute decline in organ preservation (from 26.4% in 2006 to 20.3% in 2020; P < .001). The annual rate of transanal local excisions decreased for all stages. In the subgroup of 80 607 eligible patients, the proportion of complete pathologic responses increased from 6.5% in 2006 to 18.8% in 2020 (P < .001). Conclusions and Relevance: This case series shows that rectal cancer is increasingly being managed medically, especially among patients whose treatment historically relied on proctectomy. Given the National Comprehensive Cancer Network endorsement of watch and wait, the increasing trends in organ preservation, and the nearly 3-fold increase in complete pathologic responses, international professional societies should urgently develop multidisciplinary core outcome sets and care quality indicators to ensure high-quality rectal cancer research and care delivery accounting for organ preservation.

Rectal cancer - avoiding surgery?

Nonoperative treatment of rectal cancer is gaining popularity. Several trials recently demonstrated advantages in disease-free survival with total neoadjuvant treatment (TNT) with the addition of the watch and wait (WW) strategy for locally advanced rectal cancer. On longer follow-up, an unexpected increased risk in local recurrence in the TNT group at the RAPIDO trial suggested early surgery for nonresponding tumours. The WW option is globally accepted for a complete clinical response; however, a high rate of regrowth was found in a registry with an increased risk of distant metastases, questioning the deleterious effect of deferral of surgery in this group. The short- and long-term toxic effects of neoadjuvant treatment are costs to consider in the National Comprehensive Cancer Network guidelines compared with the European Society for Medical Oncology guidelines, which favour surgery alone if good mesorectal resection is assured with increasing surgical proficiency adjusted to the precise anatomical location.

Anal Adenocarcinoma Treated in the Era of Total Neoadjuvant Therapy and Nonoperative Management.

BACKGROUND: Anal adenocarcinoma bears a treatment strategy unique to other anal cancers. OBJECTIVE: This study aimed to describe oncologic outcomes of total neoadjuvant therapy followed by watch-and-wait approach for anal adenocarcinoma. DESIGN: Retrospective analysis. SETTINGS: This study was conducted at a comprehensive cancer center. PATIENTS: Patients with anal adenocarcinoma treated between 2004 and 2019 were selected. INTERVENTIONS: Fifty-four patients received neoadjuvant therapy and were divided into 2 groups according to their treatment strategy: total neoadjuvant therapy versus single neoadjuvant modality therapy. MAIN OUTCOME MEASURES: Organ preservation, tumor regrowth, local failure, distant metastasis rates, recurrence-free survival, and overall survival. RESULTS: This study included 70 patients with anal adenocarcinoma. Fifty-four patients (77%) received neoadjuvant therapy, of whom 30 (42%) received total neoadjuvant therapy and 24 (34%) received single neoadjuvant modality. Twenty-three (33%) patients achieved complete clinical response and were managed by watch-and-wait approach. The proportion of patients able to continue to watch-and-wait approach was higher after receiving total neoadjuvant therapy (60%) compared with single neoadjuvant modality therapy (20%; p = 0.004). A tumor regrowth rate of 22% was observed in the total neoadjuvant therapy group. The 5-year overall survival rate was 70% (95% CI, 59%-83%), including 61% (95% CI, 42%-88%) for the total neoadjuvant therapy and 65% (95% CI, 48%-88%) for the single neoadjuvant modality groups. Colostomy was avoided in 50% of patients who received total neoadjuvant therapy and 83% of watch-and-wait patients. Five-year recurrence-free survival rates of 55% (95% CI, 39%-79%) and 30% (95% CI, 15%-58%) were observed in the total neoadjuvant therapy and single neoadjuvant modality groups. LIMITATIONS: Retrospective nature. CONCLUSIONS: This is the first report in the literature describing the safety and feasibility of nonoperative management for anal adenocarcinoma. Anal adenocarcinoma treated with total neoadjuvant therapy and nonoperative management achieve regrowth rates comparable to those observed in rectal cancer, with oncologic outcomes similar to those of traditional treatment strategies. See Video Abstract . ADENOCARCINOMA ANAL TRATADO EN LA ERA DE LA TERAPIA NEOADYUVANTE TOTAL Y EL TRATAMIENTO NO QUIRRGICO: ANTECEDENTES:El adenocarcinoma anal conlleva una estrategia de tratamiento único para otros cánceres anales.OBJETIVO:Describir los resultados oncológicos de la terapia neoadyuvante total seguida de observar y esperar en adenocarcinoma anal.DISEÑO:Análisis retrospectivo.AJUSTE:Este estudio se llevó a cabo en un centro oncológico integral.PACIENTES:Se seleccionaron pacientes con adenocarcinoma anal tratados entre 2004-2019.INTERVENCIONES:Cincuenta y cuatro pacientes recibieron terapia neoadyuvante y se dividieron en dos grupos según su estrategia de tratamiento: terapia neoadyuvante total versus terapia de modalidad neoadyuvante única.PRINCIPALES MEDIDAS DE RESULTADO:Preservación de órganos, recurrencia tumoral, falla local, tasas de metástasis a distancia, libre de recurrencia y supervivencia general.RESULTADOS:El estudio incluyó a 70 pacientes con adenocarcinoma anal. Cincuenta y cuatro pacientes (77%) recibieron terapia neoadyuvante, de los cuales 30 (42%) recibieron terapia neoadyuvante total y 24 (34%) recibieron modalidad neoadyuvante única. Veintitrés (33%) pacientes presentaron una respuesta clínica completa y fueron tratados con vigilancia y espera. La proporción de pacientes capaces de continuar en observar y esperar fue mayor después de recibir terapia neoadyuvante total (60%) en comparación con la terapia de modalidad neoadyuvante única (20%) ( p = 0,004). Se observó una tasa de recurrencia tumoral del 22% en el grupo de terapia neoadyuvante total. La tasa de supervivencia general a 5 años fue del 70% (IC95% 59%-83 %), incluido el 61% (IC95% 42%-88%) para la terapia neoadyuvante total y el 65% (IC95% 48%-88%) para grupos de modalidad neoadyuvante única. Se evitó la colostomía en el 50% de los pacientes que recibieron terapia neoadyuvante total y el 83% de los pacientes en observar y esperar. Se observaron tasas de supervivencia libre de recurrencia a cinco años del 55% (IC95% 39%-79%) y del 30% (IC95% 15%-58%) en los grupos de terapia neoadyuvante total y modalidad neoadyuvante única, respectivamente.LIMITACIONES:Diseño retrospectivo.CONCLUSIONES:Este es el primer informe en la literatura que describe la seguridad y viabilidad del tratamiento no quirúrgico del adenocarcinoma anal. El adenocarcinoma anal tratado con terapia neoadyuvante total y manejo no quirúrgico logra tasas de recurrencia comparables a las observadas en el cáncer de recto, con resultados oncológicos similares a las estrategias de tratamientos tradicionales. (Traducción-Dr. Fidel Ruiz Healy ).

Current status of Complementary and Alternative Medicine Interventions in the Management of Pancreatic Cancer - An Overview.

OPINION STATEMENT: Pancreatic cancer (PC) remains the deadliest cancer worldwide. Most patients are diagnosed at the advanced or metastatic stage, leading to a poor prognosis. Awareness of the limitations of current therapy and accompanying pain, depression, malnutrition, and side effects of chemoradiotherapy may lead patients and physicians towards complementary and alternative medicine (CAM). CAM refers to a diverse set of medical and healthcare practices, products, and systems that are not part of conventional Western medicine. Despite the low-quality evidence supporting the efficacy of these methods, they remain appealing due to patients' beliefs, fear of death, and the slow development of conventional therapy. Hence, the possibility of using natural products for pancreatic cancer is increasing. CAM options such as: medical cannabis, plants, fungi, herbal formulas, and injections, which originate primarily from traditional Chinese or Japanese medicine i.e. Curcuma longa, Panax ginseng, Poria cocos, Hochuekkito, Juzentaihoto, and Rikkunshito, Shi-quan-da-bu-tang/TJ-48, Huang-qin-tang, Shuangbai San, Wen Jing Zhi Tong Fang, Xiang-Sha-Liu-jun-zi-tang, Aidi injection, Brucea javanica oil emulsion/Yadanziyouru injection, Compound Kushen injection, Huachansu injection, Kangai injection and Kanglaite injections are becoming promising candidates for the management of pancreatic cancer. The abovementioned substances/medications are the most popular or potentially effective in PC treatment and consequently CAM-based adjuvant therapy through improving patients' quality of life, might be a useful addition in the treatment of pancreatic cancer patients.

Impact of photobiomodulation for prevention of oral mucositis on the quality of life of patients with head and neck cancer: a systematic review.

The aim of this study was to perform a systematic review to evaluate the impact of photobiomodulation therapy (PBMT) for the prevention of oral mucositis (OM) on the quality of life (QoL) of patients with head and neck cancer (HNC) undergoing radiation therapy. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search strategy was performed in five electronic databases (Cochrane, Embase, PubMed, Scopus, and Web of Science). The included studies assessed the QoL of patients undergoing radiation therapy (RT) for HNC and undergoing PBMT for the management of OM. Seven articles met the eligibility criteria. Data extraction was performed in the selected studies including the PBMT parameters (active medium, application procedure, wavelength, fluence, power, irradiance, irradiation time, spot size, energy per point, schedule of irradiation, and total energy). The included studies were qualitatively analyzed, and descriptive analyses were performed. Also, summary results were evaluated for group comparison analysis. All included studies confirmed a decrease in the QoL of the patients that developed OM throughout the RT progress when compared to baseline. Of the informed cases, most of the patients who received PBMT showed grades 1 and 2 OM, while the control group showed more individuals with severe forms of OM (grades 3 and 4). In this sense, patients submitted to PBMT reported better QoL at the end of the treatment compared with the control group. PBMT used for the management of OM preserves the QoL of patients with head and neck cancer.

Differential H2O2 Metabolism among Glioblastoma Subtypes Confers Variable Responses to Pharmacological Ascorbate Therapy Combined with Chemoradiation.

Glioblastoma (GBM), a highly lethal and aggressive central nervous system malignancy, presents a critical need for targeted therapeutic approaches to improve patient outcomes in conjunction with standard-of-care (SOC) treatment. Molecular subtyping based on genetic profiles and metabolic characteristics has advanced our understanding of GBM to better predict its evolution, mechanisms, and treatment regimens. Pharmacological ascorbate (P-AscH-) has emerged as a promising supplementary cancer therapy, leveraging its pro-oxidant properties to selectively kill malignant cells when combined with SOC. Given the clinical challenges posed by the heterogeneity and resistance of various GBM subtypes to conventional SOC, our study assessed the response of classical, mesenchymal, and proneural GBM to P-AscH-. P-AscH- (20 pmol/cell) combined with SOC (5 µM temozolomide and 4 Gy of radiation) enhanced clonogenic cell killing in classical and mesenchymal GBM subtypes, with limited effects in the proneural subtype. Similarly, following exposure to P-AscH- (20 pmol/cell), single-strand DNA damage significantly increased in classical and mesenchymal but not proneural GBM. Moreover, proneural GBM exhibited increased hydrogen peroxide removal rates, along with increased catalase and glutathione peroxidase activities compared to mesenchymal and classical GBM, demonstrating an altered H2O2 metabolism that potentially drives differential P-AscH- toxicity. Taken together, these data suggest that P-AscH- may hold promise as an approach to improve SOC responsiveness in mesenchymal GBMs that are known for their resistance to SOC.

Preoperative sequential short-course radiation therapy and FOLFOX chemotherapy versus long-course chemoradiotherapy for locally advanced rectal cancer: a multicenter, randomized controlled trial (SOLAR trial).

BACKGROUND: Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). METHODS: A multicenter randomized phase II trial involving 364 patients with LARC (cT3-4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45-50.4 Gy in 25-28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2-5 weeks from the last cycle of chemotherapy in the experimental arm and 6-8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. DISCUSSION: This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. TRIAL REGISTRATION: This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Perioperative Chemotherapy and Chemoradiotherapy for Patients With Resectable and Borderline Resectable Pancreatic Adenocarcinoma.

OBJECTIVES: Pancreatic ductal adenocarcinoma (PDA) is the third most common cause of cancer death in the United States. Most patients who undergo resection develop recurrence. Standard treatment confers a median overall survival (OS) of 24 months. Exposure to alternate regimens may prevent chemoresistance. This study evaluated multiagent perioperative therapy for potentially resectable PDA patients to improve OS. METHODS: A single center, phase 2, trial of patients with resectable or borderline resectable PDA. Patients received neoadjuvant therapy with induction chemotherapy (gemcitabine, docetaxel, capecitabine) for 3 cycles, chemoradiation (intensity-modulated radiation therapy with capecitabine and oxaliplatin) followed by surgery, and 2 months of adjuvant gemcitabine and oxaliplatin and 2 months of gemcitabine. The primary endpoint was OS. The secondary endpoint was recurrence-free survival (RFS). RESULTS: Thirty-two eligible patients were enrolled. Twenty-two patients underwent surgical resection. After a median follow-up of 56.8 months, mOS was 31.6 months (95% confidence interval [CI], 14.2-58.1) for all patients, 58.1 months (95% CI, 31.6 to NR) for those who completed surgery. The mRFS was 31.3 months (95% CI, 12.5 to NR). CONCLUSIONS: Perioperative therapy with GTX, chemoradiotherapy, and adjuvant GemOx/Gem resulted in promising survival of 58 months for patients who underwent resection and may represent another treatment option for PDA.

The future opportunities and remaining challenges in the application of nanoparticle-mediated hyperthermia combined with chemo-radiotherapy in cancer.

A pivotal cause of death in the modern world, cancer is an insidious pathology that should be diagnosed at an early stage for successful treatment. Development of therapeutic interventions with minimal invasiveness and high efficacy that can discriminate between tumor and normal cells is of particular interest to the clinical science, as they can enhance patient survival. Nanoparticles are an invaluable asset that can be adopted for development of such diagnostic and therapeutic modalities, since they come in very small sizes with modifiable surface, are highly safe and stable, and can be synthesized in a controlled fashion. To date, different nanoparticles have been incorporated into numerous modalities such as tumor-targeted therapy, thermal therapy, chemotherapy, and radiotherapy. This review article seeks to deliver a brief account of recent advances in research and application of nanoparticles in hyperthermia-based cancer therapies. The most recent investigations are summarized to highlight the latest advances in the development of combined thermo-chemo-radiotherapy, along with the challenges associated with the application of nanoparticles in cancer therapy. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.

Pre-treatment risk factors to predict early cisplatin-related nephrotoxicity in locally advanced head and neck cancer patients treated with chemoradiation: A single Institution experience.

OBJECTIVES: Cisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors. MATERIAL AND METHODS: We retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6-20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed. RESULTS: Of the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association. CONCLUSIONS: Identifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes.

L-Glutamine and Survival of Patients with Locally Advanced Head and Neck Cancer Receiving Chemoradiotherapy.

We previously reported that L-glutamine reduces the severity of mucositis caused by chemoradiotherapy in patients with head and neck cancer. However, the impact of glutamine on the anti-tumor effect of chemoradiotherapy remains controversial. This study, which included 40 patients, investigated whether L-glutamine influences survival. Radiation therapy (total: 66 or 70 Gy), cisplatin, and docetaxel were co-administered for a period of 6 weeks. Patients were randomly assigned to receive either glutamine (glutamine group, n = 20) or placebo (placebo group, n = 20) during the entire course of chemoradiotherapy. We compared the overall survival and progression-free survival rates between the two groups. At 5-year follow-up, 16 (80%) and 13 (72%) patients in the glutamine and placebo groups, respectively, survived (with no significant difference in overall survival [glutamine group: 55.2 ± 12.7 months vs. placebo group: 48.3 ± 21.3 months]). A total of 14 (70%) and 12 (67%) patients in the glutamine and placebo groups, respectively, did not experience disease progression (with no significant difference in progression-free survival [glutamine group: 46.7 ± 19.5 months vs. placebo group: 43.6 ± 25.2 months]). These findings indicate that L-glutamine does not influence the survival of patients with locally advanced head and neck cancer receiving chemoradiotherapy.

Clinicopathological Outcomes in Patients With Locally Advanced Rectal Cancer Undergoing Preoperative Short-Versus Long-course Chemoradiotherapy With Delayed Surgery.

BACKGROUND/AIM: We aimed to compare the clinicopathological outcomes in patients with locally advanced rectal cancer after short- or long-course concurrent chemoradiotherapy (CCRT) followed by delayed surgery. PATIENTS AND METHODS: The records of 94 patients with cT3-4N0-2M0 rectal cancer who received CCRT between 2010 and 2017 were reviewed. Short-course radiotherapy (RT) was delivered with a median total dose of 25 Gy in five fractions (n=27), and long-course RT was delivered with a median total dose of 50.4 Gy in 28 fractions (n=67). The following concurrent chemotherapy regimens were administered: 5-fluorouracil plus leucovorin in 58 and capecitabine in 24; in 12 cases agents were unknown. The median interval between CCRT and surgery was 8 weeks. Adjuvant chemotherapy was administered after surgery in 80 patients (5-fluorouracil plus leucovorin, n=54; capecitabine, n=9; other, n=14; and unknown, n=3). Propensity-score matching analysis was conducted. RESULTS: The median follow-up duration was 4.3 years. There were no statistically significant differences between the short- and long-course RT groups in sphincter preservation (85.2% vs. 92.5%, p=0.478), pathological complete remission (18.5% vs. 14.9%, p=0.905), downstaging (44.4% vs. 26.9%, p=0.159), and negative circumferential resection margin (92.6% vs. 89.6%, p=0.947) rates. No differences were found in survival outcomes between the short- and long-course groups at 3 years (overall survival: 91.8% vs. 88.1%, p=0.790; disease-free survival, 75.2% vs. 72.5%, p=0.420; locoregional relapse-free survival, 90.5% vs. 98.4%, p=0.180; and distant metastasis-free survival, 79.6% vs. 73.5%, p=0.490). Similar results were observed after PSM. CONCLUSION: Clinically, short-course CCRT may be a feasible alternative to long-course CCRT in patients with locally advanced rectal cancer.

PLK1 regulating chemoradiotherapy sensitivity of esophageal squamous cell carcinoma through pentose phosphate pathway/ferroptosis.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the most common pathological type of esophageal cancer in China, accounting for more than 90 %. Most patients were diagnosed with advanced-stage ESCC, for whom new adjuvant therapy is recommended. Therefore, it is urgent to explore new therapeutic targets for ESCC. Ferroptosis, a newly discovered iron-dependent programmed cell death, has been shown to play an important role in carcinogenesis by many studies. This study explored the effect of Polo like kinase 1 (PLK1) on chemoradiotherapy sensitivity of ESCC through ferroptosis METHODS: In this study, we knocked out the expression of PLK1 (PLK1-KO) in ESCC cell lines (KYSE150 and ECA109) with CRISPR/CAS9. The effects of PLK1-knock out on G6PD, the rate-limiting enzyme of pentose phosphate pathway (PPP), and downstream NADPH and GSH were explored. The lipid peroxidation was observed by flow cytometry, and the changes in mitochondria were observed by transmission electron microscopy. Next, through the CCK-8 assay and clone formation assay, the sensitivity to cobalt 60 rays, paclitaxel, and cisplatin were assessed after PLK1-knock out, and the nude mouse tumorigenesis experiment further verified it. The regulation of transcription factor YY1 on PLK1 was evaluated by dual luciferase reporter assay. The expression and correlation of PLK1 and YY1, and their impact on prognosis were analyzed in more than 300 ESCC cases from the GEO database and our center. Finally, the above results were further proved by single-cell sequencing. RESULTS: After PLK1 knockout, the expression of G6PD dimer and the level of NADPH and GSH in KYSE150 and ECA109 cells significantly decreased. Accordingly, lipid peroxidation increased, mitochondria became smaller, membrane density increased, and ferroptosis was more likely to occur. However, with the stimulation of exogenous GSH (10 mM), there was no significant difference in lipid peroxidation and ferroptosis between the PLK1-KO group and the control group. After ionizing radiation, the PLK1-KO group had higher lipid peroxidation ratio, more cell death, and was more sensitive to radiation, while exogenous GSH (10 mM) could eliminate this difference. Similar results could also be observed when receiving paclitaxel combined with cisplatin and chemoradiotherapy. The expression of PLK1, G6PD dimer, and the level of NADPH and GSH in KYSE150, ECA109, and 293 T cells stably transfected with YY1-shRNAs significantly decreased, and the cells were more sensitive to radiotherapy and chemotherapy. ESCC patients from the GEO database and our center, YY1 and PLK1 expression were significantly positively-correlated, and the survival of patients with high expression of PLK1 was significantly shorter. Further analysis of single-cell sequencing specimens of ESCC in our center confirmed the above results. CONCLUSION: In ESCC, down-regulation of PLK1 can inhibit PPP, and reduce the level of NADPH and GSH, thereby promoting ferroptosis and improving their sensitivity to radiotherapy and chemotherapy. Transcription factor YY1 has a positive regulatory effect on PLK1, and their expressions were positively correlated. PLK1 may be a target for predicting and enhancing the chemoradiotherapy sensitivity of ESCC.

The Auxiliary Effects of Low-Molecular-Weight Fucoidan in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy Before Surgery: A Double-Blind, Randomized, Placebo-Controlled Study.

Patients with cancer use low-molecular-weight fucoidan (LMF) as a supplement to therapy. However, most studies of LMF are in vitro or conducted using animals. Concurrent chemoradiotherapy (CCRT) is the gold standard for locally advanced rectal cancer (LARC). This study investigated the quality of life (QoL) and clinical outcomes of patients with LARC taking LMF as a supplement to neoadjuvant CCRT. This was a double-blind, randomized, placebo-controlled study. The sample comprised 87 patients, of whom 44 were included in a fucoidan group and 43 were included in a placebo group. We compared their QoL scores and clinical outcomes before treatment, and at 1 month, 2 months, and 3 months posttreatment. Pretreatment and posttreatment gut microbiota differences were also compared. Although enhanced physical well-being (PWB) at 2 months and 3 months posttreatment in the fucoidan group were observed (both P < .0125), the improvements of the Functional Assessment of Cancer Therapy for Patients with Colorectal Cancer (FACT-C) were nonsignificant (all P > .0125). Skin rash and itching and fatigue were less common in the fucoidan group (both P < .05). Posttreatment, the genus Parabacteroides was significantly more common in the gut microbiota of the fucoidan group. LMF administration improved the QoL, skin rash and itching, fatigue, and gut microbiota composition of the patients with LARC receiving CCRT.Clinical Trial Registration: NCT04342949.

Single-arm, phase II study of intra-arterial chemotherapy plus total neoadjuvant therapy to optimise complete response in distal rectal cancer: a study protocol.

INTRODUCTION: Organ preservation is now considered an acceptable alternative option in distal rectal cancer patients with clinical complete response (cCR) after neoadjuvant chemoradiation (CRT). But the cCR rate is low and about one-third of tumour will regrow, which requires more effective local treatment. CRT combined with intra-arterial chemotherapy (IAC) might be a promising approach. Additionally, total neoadjuvant therapy using FOLFIRINOX induction chemotherapy improved survival while consolidation chemotherapy improved organ preservation. We assess whether IAC plus CRT and FOLFIRINOX consolidation chemotherapy can improve the chance of organ preservation and survival in distal rectal cancer. METHODS AND ANALYSIS: This prospective, monocentric, open-label, single-arm phase II study will include 32 patients with cT3-4NanyM0 distal rectal adenocarcinoma. All patients will receive one cycle of IAC (irinotecan, raltitrexed and oxaliplatin), followed by CRT (50 Gy/25 fractions with concomitant capecitabine) and then with six cycles of FOLFIRINOX (leucovorin, 5-fluorouracil, oxaliplatin and irinotecan). After final evaluation, patients with cCR will receive non-operative management or surgery at their own discretion and others are mandatorily referred to surgery. Adjuvant chemotherapy with six cycles of mFOLFOX6 (leucovorin, 5-fluorouracil and oxaliplatin) will be used for patients with adverse pathological features. The primary endpoint is the rate of complete response (CR; pathological CR or sustained cCR≥2 years). The main secondary endpoints are toxicity, compliance, short-term and long-term oncological outcomes, surgical morbidity and quality of life. This protocol has been designed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials 2013 guidelines. ETHICS AND DISSEMINATION: This study was approved by the Academic and Ethics Committee of The Affiliated Hospital of Youjiang Medical University for Nationalities in March 2023. Trial results will be published in peer-reviewed international journals and on the ChiCTR website. PROTOCOL VERSION: Registered on 18 April 2023; version #1. TRIAL REGISTRATION NUMBER: ChiCTR2300070620.

Chemoradiotherapy plus hyperthermia (CRTH) versus chemoradiotherapy (CRT) alone in neoadjuvant treatment of soft tissue sarcoma: tumor response, treatment toxicity and disease control.

INTRODUCTION: Neoadjuvant chemotherapy and radiotherapy for the management of soft tissue sarcomas (STS) are still preferably delivered sequentially, with or without concurrent hyperthermia. Concurrent delivery of chemo-, radio- and thermotherapy may produce synergistic effects and reduce chemotherapy-free intervals. The few available studies suggest that concurrent chemoradiation (CRT) has a greater local effect. Data on the efficacy and toxicity of adding hyperthermia to CRT (CRTH) are sparse. MATERIALS AND METHODS: A cohort of 101 patients with STS of the extremities and trunk who received CRT (n = 33) or CRTH (n = 68) before resection of macroscopic tumor (CRT: n = 19, CRTH: n = 49) or re-resection following a non-oncological resection, so called 'whoops procedure', (CRT: n = 14, CRTH: n = 19) were included in this retrospective study. CRT consisted of two cycles of doxorubicine (50 mg/m2 on d2) plus ifosfamide (1500 mg/m2 on d1-5, q28) plus radiation doses of up to 60 Gy. Hyperthermia was delivered in two sessions per week. RESULTS: All patients received the minimum dose of 50 Gy. Median doses of ifosfamide and doxorubicin were comparable between CRT (75%/95%) and CRTH (78%/97%). The median number of hyperthermia sessions was seven. There were no differences in acute toxicities. Major wound complications occurred in 15% (CRT) vs. 25% (CRTH) (p = 0.19). In patients with macroscopic disease, the addition of hyperthermia resulted in a tendency toward improved remission: regression ≥90% occurred in 21/48 (CRTH) vs. 4/18 (CRT) patients (p = 0.197). With a median postoperative follow-up of 72 months, 6-year local control and overall survival rates for CRTH vs. CRT alone were 85 vs. 78% (p = 0.938) and 79 vs. 71% (p = 0.215). CONCLUSIONS: Both CRT and CRTH are well tolerated with an expected rate of wound complications. The results suggest that adding hyperthermia may improve tumor response.