Chemoradiotherapy For Cancer Research Articles

Phase II clinical trial assessing the addition of hyperthermia to salvage concurrent chemoradiotherapy for unresectable recurrent head and neck cancer in previously irradiated patients

BackgroundThis single-arm phase II trial aimed to assess the effectiveness and safety of incorporating hyperthermia into salvage concurrent chemoradiotherapy (CCRT) for previously irradiated unresectable recurrent head and neck cancer.MethodsWe enrolled patients with non-metastatic recurrent head and neck cancer who had previously undergone radiotherapy (RT) and were unfit for salvage surgery. Eligible patients received hyperthermia during salvage CCRT. RT consisted of an upfront boost with 10 Gy in 2 fractions to gross tumor volume, followed by 40 Gy in 20 fractions to clinical target volume, for a total of 50 Gy in 22 fractions. Weekly hyperthermia for 6 sessions started after RT initiation; each session lasted for 40 min, beginning within 2 h after RT and maintaining a maximum temperature of 42 ± 0.5 °C. Concurrent chemotherapy included weekly cisplatin 20 mg/m2 and docetaxel 10–12 mg/m2 for 6 weeks. Primary endpoint was overall response rate (ORR). Overall survival (OS), progression-free survival (PFS) and toxicities were evaluated.ResultsAmong 35 eligible patients, ORR was 82.9%, with complete response in 54.3%, partial response in 28.6%, stable disease in 11.4%, and progressive disease in 5.7%. After a median follow-up of 2.7 years, median OS was 32.8 months (95% confidence interval [CI], 16.7–48.9), and 2-year OS was 57.1% (95% CI, 40.6–73.6). Median PFS was 14.9 months (95% CI, 5.7–24.1), and 2-year PFS was 34.3% (95% CI, 18.6–50.0). Acute mucositis was grade 0–1 in 68.6%, grade 2 in 25.7%, and grade 3 in 5.7%. Acute dermatitis was grade 0–1 in 85.7% and grade 2 in 14.3%. No definite burn injury occurred. Grade 3–4 leucopenia, anemia, thrombocytopenia accounted for 14.3%, 14.3%, and 8.6%, respectively. Osteonecrosis was noted in 12 patients. No grade 5 toxicity was observed.ConclusionsAdding hyperthermia to salvage CCRT greatly enhances tumor response and survival rates compared to historical re-irradiation outcomes for previously irradiated unresectable recurrent head and neck cancer, with manageable toxicities.Trial registrationClinicalTrials.gov (Identifier: NCT02567383 ), Registered October 1 ,201 5 -https://www.clinicaltrials.gov/study/NCT02567383

Lipoic acid-boronophenylalanine-derived multifunctional vesicles for cancer chemoradiotherapy

Cancer remains a major health challenge, with the effectiveness of chemotherapy often limited by its lack of specificity and systemic toxicity. Nanotechnology, particularly in targeted drug delivery, has emerged as a key innovation to address these limitations. This study introduces lipoic acid-boronophenylalanine (LA-BPA) derivatives that incorporate short-chain polyethylene glycol (PEG) as a spacer. These derivatives distinctively self-assemble into vesicles under specific pH conditions, exhibiting a pH-dependent reversible assembly characteristic. Notably, these vesicles target cancer cells by binding to sialic acid via phenylboronic acid groups, subsequently depleting cellular glutathione and elevating reactive oxygen species, thereby inducing apoptosis via mitochondrial dysfunction and mitophagy. The vesicles demonstrate high efficiency in encapsulating doxorubicin, featuring a glutathione-responsive release mechanism, which present a promising option for tumor therapy. Additionally, the derivatives of the B-10 isotope, containing up to 1.6% boron, are engineered for incorporation into LPB-3-based vesicles. This design facilitates their application in boron neutron capture therapy (BNCT) alongside chemotherapy for the treatment of pancreatic cancer. Our findings highlight the potential of LA-BPA derivatives in developing more precise, effective, and less detrimental chemoradiotherapy approaches, marking an advancement in nanomedicine for cancer treatment.

Quality of life following complete clinical response to chemoradiotherapy for rectal cancer: Patient-reported outcomes.

120 Background: Complete clinical response (cCR) after neoadjuvant therapy (chemoradiotherapy/total neoadjuvant treatment) for rectal cancer may permit an organ-preserving approach with “watch and wait” (W&W) surveillance. This confers comparable survival, while avoiding the sequelae of pelvic surgery. Data on quality of life (QOL) for this cohort are lacking. Methods: Patient-reported outcomes were collated for patients on W&W following cCR in a single hospital network. Validated questionnaires evaluating surgical, radiation and chemotherapy-related QOL were completed, including Low Anterior Resection Syndrome (LARS) score, Functional Assessment of Chemotherapy: Colorectal (FACT-C), EORTC QLQ-CIPN20, EQ-5D-5L and a linear analogue and ordinal scale ranking self-perception of health. Results: From 2016-2023, 76 patients were enrolled on W&W. Median follow-up is 37 months (IQR20-63). 12 patients (15.8%) had local regrowth, of whom 11 (92%) had salvage surgery. Five patients (6.5%) developed metastases at median 8 months (IQR3-12) from W&W entry. Of 57 patients (75%) with sustained cCR on surveillance, 44 (77%) responded to structured questionnaires. Two with stomas were excluded from LARS. 74% of respondents had no LARS, 9% minor LARS and 17% major LARS. 43% reported faecal urgency and 33% faecal incontinence. 41% experienced functional impairment due to chronic chemotherapy-related side effects (Table). Median EORTC CIPN20 score was 23 (IQR20-28; possible range 19-76, high score = poor QOL). Median sensory score was 11 (IQR9-15.5, PR 9-36), median motor score 8 (IQR8-11, PR 8-32) and median autonomic score 4 (IQR3-6) for males (PR 3-12) and 2 (IQR2-2.5) for females (PR 2-8). 54% of men reported erectile dysfunction, of whom 62% experienced severe dysfunction (33% of all males). Median FACT-C score was 123.5 (IQR108-131; PR 0-136, high score = better QOL). Median overall health score was 80% (IQR70-95). 36% of patients reported difficulty with mobility, 27% with usual activities and 11% with self-care. 30% declared ongoing physical pain/discomfort, while 23% live with anxiety/depression related to their diagnosis. Overall, 86% of reported problems were mild/moderate and 14% severe/very severe. Conclusions: This study highlights self-reported QOL in patients on W&W pathway following neoadjuvant treatment of rectal cancer. It provides important insight to side-effects of treatment escalation in hope of organ preservation, and presents vital information for the counselling of future patients. Patients (n=41) Upper limb paraesthesia 12 (29%) Lower limb paraesthesia 17 (41%) Difficulty with: - Walking/standing (foot drop or impaired sensation) 10 (24%) - Stairs/sit-to-stand (leg weakness) 11 (27%) - Hot/cold differentiation 4 (10%) - Holding pen/manipulating small objects/opening jar/bottle 12 (29%) Hearing impairment 13 (32%) Blurred vision 4 (10%)

Investigating the real-world outcomes of single- versus multi-agent preoperative chemoradiotherapy for locally advanced rectal cancer: NCDB analysis from 2004-2020.

61 Background: Fluorouracil-based chemoradiotherapy is the standard initial treatment for locally advanced rectal cancer, demonstrating improved pathological response and reduced local recurrences compared to radiation alone. Fluorouracil-based chemo-radiation therapy has no impact on distant recurrences. Oxaliplatin was tested in addition to fluorouracil-based chemo-radiotherapy in clinical trials to improve pathological complete response (pCR), distant recurrence-free survival, and overall survival. The trial results are conflicting. In this study, we aim to compare single-agent (SA) versus multi-agent (MA) chemotherapy using real-world data from the National Cancer Database (NCDB). Methods: The NCDB was used to identify 39,667 patients with rectal cancer who received concurrent chemoradiotherapy between 2004 and 2020. We compared patients who received SA chemotherapy with those who received MA concurrent chemotherapy. The primary outcomes of interest were overall survival and pCR. The groups were compared using univariate analysis and Cox proportional hazard models to adjust for potential confounding factors. Results: Of 39,667 patients with rectal cancer, 24,452 received single-agent (SA) chemotherapy and 14,215 received multi-agent (MA) chemotherapy. Patients in the SA group were of advanced age, had a greater number of comorbidities (as calculated by the Charleson-Dayo score), were treated within community facilities, had a higher income status, were covered by government insurance, were situated on the east coast, and had lower educational attainment compared to those in the MA group (p<0.05). SA group had higher T4 and N1 disease, however MA group had more N2 disease. Upon survival analysis, patient in MA group had higher survival (41.2 vs 38.9 months, p=0.005), however pCR was significantly higher in SA group (10.4% vs 6.4%, p<0.001). Conclusions: MA chemoradiotherapy for rectal cancer improves survival, with the SA regimen showing enhanced complete pathological response. Differences in baseline characteristics may explain the outcomes. While MA chemotherapy offers modest overall survival benefits, potential toxicity needs to be considered and confirmed in future studies. Comparison between single agent vs multi-agent chemo-radiotherapy group. Outcome Single-agent chemotherapy Multiagent chemotherapy Chi Squared p-value No readmission within 30 days of surgical discharge 22,727 (89.3 %) 12,921 (90.9 %) <0.001 30-day mortality after surgery 360 (1.5 %) 59 (0.5 %) <0.001 90-day mortality after surgery 716 (3.0 %) 158 (1.3%) <0.001 Median duration of surgical admission 6.0 5.0 <0.001 Median survival-vital = deceased (months) 38.9 41.2 0.005 Median survival-vital = alive (months) 66.9 52.0 <0.001 Pathological complete response (pCR) 2,644 (10.4%) 904 (6.4%) <0.001

A prospective multi-site translational study investigating the association of gut microbiome (GM) diversity with pathological complete response (pCR) after neoadjuvant treatment in early stage rectal and esophageal cancer.

TPS849 Background: The diversity of the GM is defined as the number and relative abundance distribution of distinct types of microorganisms colonizing within the gut. Studies have suggested that dysbiosis of the GM confers a predisposition to certain malignancies and impacts response to immunomodulating therapies. The influence of the GM diversity on the pathological response after neoadjuvant chemotherapy and radiotherapy is unclear. Some studies have suggested that the GM may offer predictive biomarkers for response to chemoradiation in rectal cancer. Other studies in early-stage rectal cancer patients indicated an association between GM diversity and pathological outcomes following neo-adjuvant therapy (NAT). We hypothesize that a more diverse GM constitution at baseline leads to an improved pathological response at the time of definitive surgery. Methods: We designed a cross-institutional translational study investigating the impact of the GM diversity on the efficacy of NAT in GI cancers by assessing its association with pathological response. The study population includes patients with early-stage rectal or esophageal cancer due to commence NAT (including chemotherapy and chemoradiation) who are planned for definitive surgery. Exclusion criteria includes prior allogenic tissue/solid organ transplantation and prior receipt of anti-cancer therapy. The study assessments include fecal sampling of the GM prior to NAT, upon completion and again six months post completion of therapy. Fecal samples are analysed by 16S RNA sequencing. Pathological response will be examined at time of surgery and patients will be classified as responders (complete pathological response) or non-responders. The primary endpoint of the study is to examine the association between the GM diversity and pathological response. Exploratory analysis will include the assessment of the association between cf-DNA and the GM diversity as well as an assessment of the association between cf-DNA at baseline and pCR. Species richness (Alpha Diversity) will be analysed using the Shannon diversity index and Jaccard similarity index will be used to calculate beta diversity. Following planned study recruitment, classification and clustering analysis will be performed with Principal Component Analysis (PCA) and Random Forest analysis. Logistic regression analysis adjusting for potential confounding factors will be employed to assess the primary endpoint of the association between GM and complete pCR in the final statistical analysis. Adjusted odds ratios (OR) and 95% confidence intervals will be presented. This trial accrued 11 patients between May 2023 and Sept 2024. Out of the 11 patients enrolled, 9 patients have undergone their planned surgery. We are expecting to have 30 patients accrued prior to Jan 2025.

Comparison of long-term outcomes for neoadjuvant chemoradiation (NA-CRT) followed by surgery versus (V) definitive chemoradiation (D-CRT) in localized gastroesophageal cancer (GEC): A single-center analysis.

371 Background: The therapeutic approach in locally advanced GEC is evolving. NA-CRT followed by surgery has been recommended based on the CROSS trial. The SANO trial reports active surveillance may be an alternative in clinically complete response after D-CRT in both squamous cell carcinoma (SCC) and adenocarcinoma (AC). SCC and AC in GEC are different diseases with differences in tumor location, etiology, and biology. Despite the evolving landscape, there still may be a role for both CROSS and SANO approaches. In our large observational cohort study, we sought to compare the long-term outcomes in localized GEC across all histological subtypes treated with NA-CRT+Surgery V D-CR+Surveillance. Methods: A retrospective analysis comparing NA-CRT + surgery V D-CRT in localized GEC between 2007-2023 treated at the Princess Margaret Cancer Centre was completed. Baseline characteristics including age, gender, race, performance status and Charlson Comorbidity index (CCI) were reviewed. The primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS), respectively and to compare these outcomes in both histologies. Cox proportional hazards analysis and Kaplan-Meier methods were employed. Outcomes were adjusted for baseline characteristics. Results: There were 529 patients (pts) included, 321 (61%) received NA-CRT+Surgery and 208 (39%) D-CR+Surveillance. Median age was 64yrs, 75% were male and 66% had N1+ disease. The proportion of pts with SCC treated with NA-CRT+Surgery and D-CR+Surveillance was 25% and 63%, respectively. There was a statistically significant difference in median OS and DFS between pts who received NA-CRT+surgery and D-CRT+surveillance (Table). Multivariate regression analysis shows a significant association between OS and age (adjusted HR 1.02, p=0.005), male sex (HR 1.55, p=0.003) but no significant association between OS and CCI (HR 1.1 p=0.36). In our subgroup analyses, there was no statistically significant difference in OS (p=0.33) and DFS (p=0.18) between SCC and AC. However, this was significant in D-CRT (OS p<0.0001, DFS p<0.001) favoring SCC. Conclusions: In contrast to the SANO trial, we found that NA-CRT+surgery was associated with a significantly better OS and DFS compared to D-CRT when subtypes were combined. However, in the D-CRT subgroup, SCC was associated with improved OS and DFS compared to AC. Thus, we continue to recommend current approaches in SCC. Awaited updates from SANO will inform whether active surveillance may also be appropriate in pts with AC subtype. Median (95% CI)NA-CRT Surgery Median (95% CI)D-CRT Log-rank test p-value OS (mo) 28.2 (15.1, 57.6) 15.6 (7.7, 33.7) P=<0.0001 DFS (mo) 17.9 (9.6, 40.8) 9.4 (5.0, 20.7) P=<0.0001 pathCR (%) 14 - R0 resection (%) 89 -

Adjuvant chemotherapy or chemo-radiation in gallbladder cancer: A phase III randomized controlled study (ACCELERATE trial).

519 Background: Role of adjuvant therapy in gallbladder cancer is still evolving and no prospective trial has compared chemotherapy (ChT) alone to combination of chemotherapy and chemo-radiation (CRT). We designed this trial to answer whether adding CRT to ChT improves relapse free survival. Methods: In this open-label, multicentric, phase 3, non-inferiority academic trial, operated gallbladder cancers (R0 or R1) patients were randomized to physicians choice of ChT alone (either 6 cycles of mGemOx- Gemcitabine 900 mg/m2 and oxaliplatin 80 mg/m2 IVI days 1 and 8 every 3 weeks or GemCis- Gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 1 and 8 every 3 weeks) or 3 cycles of physicians choice of ChT (as above) followed by CRT (radiation 45Gyin 25 fractions in 5 weeks with concurrent oral capecitabine in the dose of 825 mg/m2 twice a day on days of radiation and further 2-3 cycles of mGemOx or GemCis. The primary endpoint was the relapse free survival. Planned sample size was 100 subjects in each arm. Results: Between April 2018 and January 2021, 137 patients were screened, and 94 eligible patients were randomized, 49 (52.1%) in chemotherapy alone arm (standard-arm1) and 45 (47.9%) in chemotherapy plus chemo-radiation arm (experimental-arm 2). Slow accrual led to premature closure of trial. COVID pandemic might have contributed to that. Baseline characteristics were well balanced (like, sex, presenting symptoms, ECOG PS, duration of symptoms, comorbidities, location of tumour in GB, presence of gallstone disease, and tumour markers were well balance in both groups) except that a greater number of patients had deranged baseline LFTs in arm1 and there was a trend towards higher numbers of stage IIA in arm 1. The median age was 55 years (range 27-73 years). Females constituted 32 in each group. 43 and 45 patients had ECOG PS of 0-1 in arm 1 and arm 2 respectively. One patient in arm 1 was ineligible. All had R0 resection. Incidences of dose reductions and dose delays were similar. A greater number of patients in arm 1 experienced diarrheal episodes (p=0.021) and peripheral neuropathy (0.001). 42 (85.7%) patients in arm 1 and 28 (62.2%) patients in arm completed 5-6 cycles. 18 (36.73%) and 23 (51.11%) died till last follow up. 14 (28.57%) and 20(44.44%) died because of disease progression. One patient in each arm died of toxicity. The primary end point of study, relapse free survival was not estimable in arm 1 and was 34.39 months in arm 2 (p=0.202). Median overall survival was not estimable in arm 1 and was 34.56 months in arm 2 (p=0.123). Mean RFS was 51.96 Vs 43.99 months in arm 1 and arm 2 respectively. Conclusions: This trial suggests that addition of CRT to ChT doesn’t improve outcome in resected gallbladder cancer compared to ChT alone. A larger trial is needed to address this issue. Clinical trial information: CTRI/2018/04/013218.

Time dependency for human papillomavirus circulating tumor DNA detection after chemoradiation as a prognostic biomarker for localized anal cancer.

While detection of circulating tumor DNA (ctDNA) weeks after surgery is linked to recurrence for other solid tumors, the optimal time point for ctDNA assessment as a prognostic biomarker following chemoradiation for anal cancer is undefined. Patients with stages I-III anal cancer treated with chemoradiation between 12/2020-5/2024 were evaluated for HPV ctDNA status at baseline, at the end of chemoradiation, and during surveillance using a droplet digital HPV ctDNA PCR assay targeting HPV E6 and E7 oncogenes for 13 oncogenic HPV types. Median recurrence-free survival (RFS) according to HPV ctDNA status was estimated via Kaplan-Meier and compared using a log-rank test. Detection of HPV ctDNA at ≥3 months after chemoradiation was associated with recurrence (80% versus 2%; odds ratio 168, 95% CI 13.6-2080; p<.0001) and inferior RFS (4.9 months versus not reached (NR); hazard ratio (HR) 39.2, 95% CI 4.6-330; p<.0001) relative to HPV ctDNA-negative status. Sensitivity and specificity for recurrence according to HPV ctDNA detection were 89% and 95%, respectively, with positive and negative predictive values of 80% and 98%, respectively. Differences in RFS according to HPV ctDNA status were not observed at the end of treatment (median RFS NR for both; HR 1.6, 95% CI .35-7.4; p=.48). With a novel, highly sensitive assay, detection of HPV ctDNA at least 3 months after chemoradiation was associated with unfavorable survival. Future clinical trials should incorporate this 3-month post-treatment time point to identify patients with HPV-positive anal cancer at elevated recurrence risk according to HPV ctDNA status.

Impact of chemoradiotherapy for first primary lung cancer on the prognosis and re-chemoradiotherapy sensitivity of second primary lung cancer

BackgroundDespite undergoing surgery and chemoradiotherapy, patients with first primary lung cancer (FPLC) remain at risk for second primary lung cancer (SPLC), which is associated with a poor prognosis. The effects of FPLC chemoradiotherapy on SPLC prognosis and its sensitivity to re-chemoradiotherapy have not been adequately investigated.MethodsThis cohort study analyzed data from 23,827 patients who underwent FPLC surgery during 1973–2021, drawn from the Surveillance, Epidemiology, and End Results database. Among these, 5,302 FPLC patients developed SPLC within 5 years of their initial diagnosis. We employed the Fine-Gray competitive risk model, Cox proportional hazards model, and restricted mean survival time analysis to assess the effects of FPLC radiotherapy and chemotherapy on SPLC risk and survival differences.ResultsThe competitive risk model indicated that FPLC radiotherapy and chemotherapy did not significantly change the risk of developing SPLC. However, the Cox proportional hazards model revealed that FPLC radiotherapy was associated with decreased overall survival (OS; HR=1.251, P&amp;lt;0.001) and cancer-specific survival (CSS; HR=1.228, P=0.001) in patients with SPLC. Conversely, FPLC chemotherapy was linked to improved OS (HR=0.881, P=0.012) in this population. Patients with SPLC who received combined chemoradiotherapy for FPLC exhibited significantly reduced survival times (OS: HR=1.157, P=0.030; CSS: HR=1.198, P=0.018), a finding confirmed across multiple models. For SPLC patients with prior FPLC chemoradiotherapy, subsequent SPLC radiotherapy significantly improved prognosis. Notably, this benefit is even more pronounced in patients who have not received prior chemoradiotherapy. While SPLC chemotherapy enhanced OS for patients who did not receive FPLC chemotherapy, it was associated with reduced CSS for those who had.ConclusionsOverall, FPLC chemoradiotherapy influences SPLC prognosis and influences sensitivity to treatment. Tailoring SPLC management to FPLC treatment regimens may improve survival outcomes.

Simultaneous integrated boost to lateral pelvic lymph nodes during chemoradiotherapy in high-risk rectal cancer.

Preoperative chemoradiotherapy combined with total mesorectal excision (TME) is astandard treatment for locally advanced rectal cancer (LARC). However, lateral pelvic lymph nodes (LPLNs) are often inadequately treated with standard regimens. This study examines the treatment and postoperative outcomes in LARC patients receiving asimultaneous integrated boost (SIB) for LPLNs during long-course chemoradiotherapy. This retrospective study included high-risk LARC patients (UICC, "Union Internationale Contre le Cancer", stageIII) treated with preoperative chemoradiotherapy and SIB to LPLNs. Radiotherapy was delivered to the primary tumor and elective volumes with 50.4 Gy in 28fractions, and anSIB with amedian dose of 60.2 Gy was administered to clinically positive LPLNs. TME quality and postoperative complications were assessed using MERCURY and Clavien-Dindo, respectively. Time-to-event data were analyzed according to Kaplan-Meier. Between 2019 and 2023, 27patients with high-risk LARC and LPLN metastases were treated with chemoradiotherapy. After amedian follow-up of 19months, 2‑year overall survival was 80%, disease-free survival 80%, and local control of dose-escalated lymph nodes 100%. Three patients were managed nonoperatively after aclinical complete response on endoscopy and imaging. Of the 22patients who had surgery, only one had complications higher than Clavien-DindogradeI; TME was graded as MERCURYI in 73%. The SIB approach for LPLNs in LARC is feasible, does not increase postoperative morbidity, and achieves excellent local control. This study supports the consideration of dose-escalated radiotherapy for LPLNs to address high local recurrence risks.

Changes in swallowing response on patients undergoing chemoradiotherapy for head and neck cancer

PurposeChemoradiotherapy (CRT) for head and neck cancer (HNC) often causes dysphagia. The risk of dysphagia increases during CRT tends to become more severe after finishing CRT, and persists for a few weeks thereafter. Thus, understanding the changes in swallowing physiology during and immediately after CRT is essential. This study aimed to clarify the changes in the swallowing response during and early after CRT and identify associated factors.MethodsThis retrospective study enrolled 107 patients with HNC who underwent CRT. We measured pharyngeal delay time (PDT) and laryngeal elevation delay time (LEDT) as indicators of the timing of the swallowing response at three time points: at CRT initiation (baseline), at 40-Gy irradiation during CRT (mid-CRT) and within 2 weeks following the completion of CRT (early post-CRT) as primary outcomes; and subgroup analyses based on clinical parameters, such as tumor sites, T stage, N stage, and opioid use at 40-Gy irradiation as secondary outcomes.ResultsBoth PDT and LEDT were significantly prolonged between baseline and mid-CRT (PDT: p = 0.003, LEDT: p = 0.002) and between baseline and early post-CRT (PDT, p = 0.001; LEDT, p < 0.001). N2c/N3 and opioid use at 40-Gy irradiation showed prolonged PDT and LEDT at mid-CRT and early post-CRT.ConclusionPDT and LEDT were prolonged at mid-CRT irradiation and further extended at early post-CRT. Additionally, N2c/N3 involvement, which typically necessitates bilateral neck irradiation fields and opioid use at mid-CRT, may constitute as risk factors for a delayed swallowing response.

Comprehensive Evaluation of Inflammatory Biomarkers in Cervical Cancer Treated with Chemoradiotherapy.

Objective: Inflammatory biomarkers have been shown to possess both prognostic and predictive significance in various cancers. Among the emerging biomarkers, the pan-immune-inflammation value (PIV) has recently been introduced as a novel indicator representing both the immune response and the systemic inflammatory state. This study aims to comprehensively evaluate the predictive value of inflammatory biomarkers on survival outcomes in cervical cancer patients undergoing chemoradiotherapy. Methods: A total of 90 patients who had undergone chemoradiotherapy for cervical cancer were included. Data on demographics, treatment protocols, pre-treatment blood parameters, and survival outcomes were collected. The association between inflammatory biomarkers and survival outcomes was investigated through univariate and multivariate analyses. Results: The univariate analysis identified the following as predictors of progression-free survival (PFS): neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), systemic immune-inflammation index (SII), PIV, C-reactive protein (CRP), albumin, and tumor size. Multivariate analysis revealed that only the PIV significantly predicted PFS (HR 3.05, 95% CI 1.0 to 9.3, p = 0.04). In the univariate analysis, several variables were predictive of overall survival (OS), including NLR, PLR, MLR, SII, PIV, CRP, LDH, albumin, tumor size, and Eastern Cooperative Oncology Group Performance Status (ECOG PS). Multivariate analysis revealed CRP (HR 3.41, 95% CI 1.5 to 7.7, p = 0.003) and ECOG PS (HR 4.78, 95% CI 1.3 to 17.3, p = 0.01) predictive of OS, with PIV approaching statistical significance (HR 2.56, 95% CI 0.8 to 7.6, p = 0.09). Conclusions: This study provides the first comprehensive analysis of the association between cervical cancer and various inflammatory biomarkers. Many of these biomarkers have demonstrated predictive value for survival outcomes in patients with cervical cancer undergoing definitive chemoradiotherapy. Among the biomarkers evaluated, CRP and PIV were identified as the most predictive, warranting further exploration in future research.

Patient-reported quality of life and adherence outcomes after integrating exclusive liquid meal replacement in patients with head and neck cancer undergoing chemoradiation: results from a phase II study.

Preventing malnutrition during chemoradiation (CRT) for head and neck cancer is critical maximizing quality of life (QOL). We sought to assess patient-reported QOL outcomes after integrating exclusive liquid meal replacement with Soylent, a novel meal replacement agent, in patients with head and neck cancer undergoing CRT. Patients undergoing definitive or adjuvant concurrent CRT for locally advanced head and neck cancer enrolled on our single-institution, prospective phase II protocol evaluating nutritional replacement with Soylent. Patients who reached 5% body weight loss during CRT were transitioned to Soylent meal replacement for all nutritional needs. Patients who reached 10% body weight loss were recommended for gastrostomy tube (G-tube) placement. UW-QOL and FACT-H&N questionnaires assessed patient-reported QOL prior to the receipt of CRT and following conclusion of CRT. Paired t-test or Wilcoxon signed-rank test were performed to assess for differences between scores at each follow-up time point and baseline. Of the 60 enrolled patients, 51/60 (85%) lost 5% of their pre-treatment body weight. Among these patients, 48/51 (94%) were successfully transitioned to Soylent. 22/48 patients subsequently lost 10% of their pre-treatment body weight, and 3/22 (14%) underwent G-tube placement with the remainder declining. This resulted in an overall G-tube rate of 5%. Among the 41 patients evaluable for QOL data, the nadirs for overall and health-related UW-QOL were reached at 1 month and rebounded to exceed baseline by 6 months. FACT-H&N survey scores were reduced from 32 at baseline to 20 at 1 month (adjusted p<0.001) and 26 at 3 months (adjusted p<0.001), but increased to 29, 30, and 27 at 6, 12, and 18 months, without significant differences as compared to baseline (adjusted p>0.38 for all). We report high patient adherence and a 5% G-tube placement rate with exclusive meal replacement with Soylent in patients undergoing concurrent CRT for head and neck cancers.

Prognostic Value of Tumor Regression Grade Combined with Pathological Lymph Node Status in Initially Node-Positive Rectal Cancer Treated with Neoadjuvant Chemoradiotherapy

Background The prognostic value of tumor regression grade (TRG) after neoadjuvant chemoradiotherapy for rectal cancer is inconsistent in the literature. Both TRG and post-therapy lymph node (ypN) status could reflect the efficacy of neoadjuvant therapy. Here, we explored whether TRG combined with ypN status could be a prognostic factor for MRI-based lymph node-positive (cN+) rectal cancer following neoadjuvant chemoradiotherapy. Methods 671 cN + rectal cancer patients who received neoadjuvant chemoradiotherapy followed by radical resection were enrolled. Patients were innovatively divided into three groups based on TRG and ypN status: TRG0-1N0, TRG2-3N0 or TRG0-1N+, TRG2-3N+. Kaplan–Meier method and log-rank test were used to compare the disease-free survival (DFS) and overall survival (OS) among three groups. Univariate and multivariate analyses were performed to explore the prognostic value of the modified TRG in cN + rectal cancer following neoadjuvant chemoradiotherapy. Results The mean duration of follow-up was 30.4 months. Significant survival differences were observed among the three groups. The 3-year DFS were 83.0%, 69.2% and 55.9%, respectively. The 5-year OS were 83.5%, 80.4% and 57.8%, respectively. TRG combined with ypN status was an independent predictor for both DFS and OS in multivariate analysis. Conclusion TRG combined with ypN status is a novel prognostic factor in cN + rectal cancer following neoadjuvant chemoradiotherapy, which assists clinicians make appropriate decisions regarding postoperative treatment and surveillance.

Do not expect an endoluminal complete response to identify a pathologic complete response in rectal cancer!

To examine the relationship between endoluminal and pathologic complete response after chemoradiotherapy for rectal cancer and identify predictors of a pathologic complete response. The anatomic pathology reports of 102 consecutive patients with rectal cancer who underwent neoadjuvant chemoradiotherapy followed by proctectomy between 2013 and 2017 were reviewed for the presence or absence of endoluminal complete response. The presence of endoluminal complete response was compared with the anatomopathological stage. The residual lesion area was compared with the final pathologic stage to identify predictors of complete response. Of 102 patients, 20 (19.6 %) achieved a pathologic complete response (ypT0N0). Of these, 9 (45 %) did not achieve an endoluminal complete response. The presence of endoluminal complete response had a sensitivity of 55.00 %, specificity of 96.34 %, and accuracy of 88.24 % to identify ypT0N0. The presence of endoluminal complete response, residual lesion area ≤ 4 cm2, and tumor located in the mid-rectum were associated with pathologic complete response (ypT0N0). Almost half of the patients who had a pathologic complete response did not achieve an endoluminal complete response. Tumors located in the mid-rectum with a residual size of ≤ 4 cm2 and the presence of endoluminal complete response were significantly associated with the achievement of ypT0N0.

Neoadjuvant Concurrent Chemoradiation and Esophagectomy for Esophageal Cancer: Outcomes With New-Onset Atrial Fibrillation.

This illustrates the outcomes of patients with esophageal cancer undergoing neoadjuvant concurrent chemoradiation and esophagectomy, specifically focusing on those who develop new-onset atrial fibrillation (NOAF). Statistically significant findings (p < 0.05, dark red) increased mortality and ventricular fibrillation, as well as trends of (p > 0.05, light red) myocardial infarction and pericardial effusion among NOAF patients. The data emphasize the significant cardiovascular risks associated with NOAF in this population.

Prophylactic gastrostomy tube during chemoradiation for head and neck cancer decreases weight loss but increases rate of tube use beyond six months.

The role of prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement in head and neck cancer (HNC) patients treated with chemoradiation remains controversial and varies by center. To evaluate the impact of prophylactic PEG tube placement in patients undergoing chemoradiation for HNC PEG tube use for more than 6months and weight loss. This single-institution retrospective study included 502 patients with head and neck cancer. Concurrent Chemoradiation (CCRT) and prophylactic PEG tube placement. Univariate analyses were performed to determine risk factors for long term PEG tube and weight loss. Outcomes that were significantly associated with prophylactic PEG were selected for a multivariate analysis. The Kaplan-Meier method was used to estimate survival and the time to PEG removal, with comparisons between groups analyzed by log-rank tests. The global health status score from the EORTC QLQ30 was utilized to assess impact on quality of life. Significantly higher weight loss was seen with the following variables: 1) omitting prophylactic PEG tube (p<0.00001), 2) younger age (p=0.0032), and 3) adjuvant CCRT (p=0.0005). There was significantly higher risk of feeding tube duration longer than 6months in those who: received prophylactic PEG tube (p<0.0001) and were older than the median age of 60.8years (p=0.0165) on multivariate analysis. Prophylactic PEG tube was not associated with improved global health status, overall survival, or progression-free survival on univariate analysis. Prophylactic feeding tubes significantly decreased weight loss during treatment. Prophylactic PEG tube and older than median age was significantly associated with higher risk of feeding tube duration longer than 6months.

A simplified scoring system for predicting treatment response in limited-stage small-cell lung cancer (EAST score).

This study aimed at developing a scoring system (EAST score) to predict recurrence after chemoradiotherapy in limited-stage small-cell lung cancer (LS-SCLC). Treatment-naïve LS-SCLC patients receiving concurrent chemoradiotherapy (CCRT) (N = 234) or sequential chemoradiotherapy (N = 53) were retrospectively reviewed. Using data from CCRT population, clinical and radiological variables associated with disease progression were identified. Selected variables were assigned numerical scores based on their estimated hazard ratios (HRs), and the EAST score was established. EAST score incorporated N3 disease and serum biomarkers (lactate dehydrogenase, pro-gastrin-releasing peptide, and cytokeratin-19 fragment). In the CCRT population, progression-free survival (PFS) was significantly shorter in the high-risk group (EAST score ≥ 2) than the low-risk group (EAST score ≤ 1) (median, 9.4 months vs. 20.6 months; HR [95% confidence interval (CI)], 2.09 [1.50-2.91]). As for the model performance, the 1- and 2-year area under the curve values for PFS were 0.68 and 0.65, respectively. Overall survival was also shorter in the high-risk group (HR [95% CI], 1.49 [1.02-2.16]). Similar trends were observed in the sequential chemoradiotherapy population (HR for PFS [95% CI], 2.43 [1.07-5.53]). EAST score effectively predicts recurrence risk in LS-SCLC, demonstrating the necessity for developing new treatment strategies for high-risk patients.

Utility of lymphocyte-to-monocyte ratio and pretreatment tooth extraction in intra-arterial chemoradiotherapy for oral cancer to prevent osteoradionecrosis of the jaw

The objective of this study was to evaluate the utility of inflammation-based prognostic scores (IBPS) in predicting ORN among patients undergoing superselective intra-arterial chemoradiotherapy (SSIACRT). This retrospective cohort study examined the medical records of 54 patients with advanced oral cancer (stage 3 or 4) treated with SSIACRT. The predictor variable was IBPS. The main outcome variable was onset of ORN. Covariates comprised sex, median age, tooth status, tumor size, and pretreatment tooth extraction with professional oral care (pretreatment tooth extraction). For each factor, cumulative incidence and univariate and multivariate analyses of ORN incidence were performed. The cumulative incidence of ORN in patients with pre-treatment lymphocyte-to-monocyte ratio (LMR < 4.95vs LMR ≥4.95, P = 0.01) and pretreatment tooth extraction (no vs. yes, P = 0.03) was significantly different. Univariate and multivariate analyses identified pre-treatment LMR cutoff values < 4.95 and pre-treatment tooth extraction as significantly associated with the development of ORN. Pretreatment tooth extraction reduced the incidence of ORN in low LMR group (P = 0.04). LMR is a useful biomarker to predict ORN in SSIACRT. Pretreatment tooth extraction was a useful treatment to prevent ORN. Pretreatment extraction with LMR may be important for the prevention of ORN in SSIACRT.

Strategies to Overcome Intrinsic and Acquired Resistance to Chemoradiotherapy in Head and Neck Cancer

Definitive chemoradiotherapy (CRT) is a cornerstone of treatment for locoregionally advanced head and neck cancer (HNC). Research is ongoing on how to improve the tumor response to treatment and limit normal tissue toxicity. A major limitation in that regard is the growing occurrence of intrinsic or acquired treatment resistance in advanced cases. In this review, we will discuss how overexpression of efflux pumps, perturbation of apoptosis-related factors, increased expression of antioxidants, glucose metabolism, metallotheionein expression, increased DNA repair, cancer stem cells, epithelial-mesenchymal transition, non-coding RNA and the tumour microenvironment contribute towards resistance of HNC to chemotherapy and/or radiotherapy. These mechanisms have been investigated for years and been exploited for therapeutic gain in resistant patients, paving the way to the development of new promising drugs. Since in vitro studies on resistance requires a suitable model, we will also summarize published techniques and treatment schedules that have been shown to generate acquired resistance to chemo- and/or radiotherapy that most closely mimics the clinical scenario.