Cisplatin-based Concurrent Chemoradiotherapy Research Articles

Role of adjuvant chemotherapy after concurrent chemoradiotherapy in patients with locally advanced cervical cancer.

Aims: With the useof concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC), survival outcomes are still not optimal. This studywas designedto evaluate the efficacy and safety of adjuvant chemotherapy (ACT) for patients with LACC after treatment with CCRT. Methods: Patients diagnosed with stage IIA-IIIB LACC, were retrospectively analyzed. All patients received cisplatin-based CCRT and were divided into two groups: ACT after CCRT (CCRT+ACT group) and observation after CCRT (CCRT group). Overall survival (OS), progression-free survival (PFS) and adverse effects wererecorded and analyzed. Results: In total, 375 patients were included; 262 patients accepted ACT after CCRT while the remaining 113 patients chose observation. With a median follow-up of 40months, no significant differences were found in the OS rates for patients in theCCRT+ACT and CCRT groups at 1year, 3years and the end of follow-up. There was alsono significant discrepancy in PFS between groups. Subgroup analysis showed theInternational Federation of Gynecology and Obstetrics (FIGO) stage and age had negligible influence on both OS and PFS. Acute adverse events (grades3-4) happened more frequently in CCRT+ACT group than in the CCRT group, with significant differences in neutropenia, anemia and creatinine. Conclusion: ACT after CCRT did not show benefit in survival but did induce some adverse effects. Therefore, this regimen is not recommended unless further large-scale randomized controlled trials are executed.

Concurrent Chemoradiotherapy With Nedaplatin Versus Cisplatin in Patients With Stage IIB-IVA Cervical Cancer: A Randomized Phase III Trial.

BackgroundIn this trial, we aimed to assess the efficacy and safety of radiotherapy with nedaplatin or cisplatin in patients with locally advanced cervical cancer.MethodsWe conducted an open-label, non-inferiority, phase III, randomized, controlled trial. Eligible patients with stage IIB-IVA cervical carcinoma were randomly assigned to receive either nedaplatin or cisplatin for two cycles concurrently with radiotherapy. We reported the therapy-associated harms and survival. The study was registered with chictr.org.cn, number ChiCTR1800020527.ResultsWe randomly assigned 68 patients to nedaplatin-based or cisplatin-based concurrent chemoradiotherapy. Study treatment was stopped early after a data analysis found a higher number of patients suffered severe hematologic harms in the nedaplatin group than in the cisplatin group. Patients in the nedaplatin group had a significantly higher frequency of grade 3-4 neutropenia (19·4% vs. 13%; P < 0·001), severe thrombocytopenia (16·1% vs. 4·3%), and grade 1-2 anemia (51·6% vs. 43·5%) than patients in the cisplatin group. The 1-year PFS and OS in the nedaplatin and cisplatin groups were similar.ConclusionOur findings showed that nedaplatin-based concurrent chemoradiotherapy expressed remarkably higher severe hematologic harms which were mortal. Though the results were negative, the experiences and lessons we learned from it were important.

Effect of Concurrent Chemoradiotherapy With Nedaplatin vs Cisplatin on the Long-term Outcomes of Survival and Toxic Effects Among Patients With Stage II to IVB Nasopharyngeal Carcinoma

Nedaplatin-based concurrent chemoradiotherapy (CCRT) regimen at 2 years was noninferior to cisplatin-based regimen in patients with locoregional, stage II to IVB nasopharyngeal carcinoma (NPC) and was associated with fewer late adverse events, but longer-term outcomes and toxicity are unclear. To evaluate the 5-year outcomes and late toxicity profile of nedaplatin-based CCRT in patients with locoregional, stage II to IVB NPC. This 5-year follow-up secondary analysis of an open-label, noninferiority, multicenter randomized clinical trial enrolled patients with nonkeratinizing stage II to IVB NPC between January 16, 2012, and July 16, 2014, with a median follow-up duration of 78 months (IQR, 3-99 months). Data analysis was conducted from November 10, 2020, to July 8, 2021. Patients were randomly assigned (1:1) to receive nedaplatin (100 mg/m2)- or cisplatin (100 mg/m2)-based chemotherapy every 3 weeks for 3 cycles concurrently with intensity-modulated radiotherapy. The primary end point was progression-free survival (PFS). Secondary end points were overall survival, distant metastasis-free survival, and locoregional relapse-free survival. A total of 402 eligible participants were enrolled (median [IQR] age, 45 [18-65] years; 302 [75.1%] male). Patients were randomly assigned to receive nedaplatin- or cisplatin-based CCRT (n = 201 for each): 196 patients (97.5%) started nedaplatin-based CCRT and 197 patients (98.0%) started cisplatin-based CCRT. Intention-to-treat analysis demonstrated a 5-year progression-free survival rate of 81.4% (95% CI, 75.9%-86.9%) for the cisplatin group and 79.8% (95% CI, 74.1%-85.5%) for nedaplatin group, with a difference of 1.6% (95% CI, -6.3% to 9.5%; P = .002 for noninferiority). No significant survival differences were observed between the cisplatin and nedaplatin groups for 5-year overall survival (89.4% vs 88.8%, P = .63), distant metastasis-free survival (85.9% vs 90.4%, P = .17), and locoregional relapse-free survival (92.6% vs 89.6%, P = .17) rates. The cisplatin group had a higher incidence of grade 3 and 4 auditory toxic effects than the nedaplatin group (35 [17.7%] vs 21 [10.5%], P = .04). In this secondary analysis of a randomized clinical trial, long-term analysis confirmed that nedaplatin-based CCRT could be regarded as an alternative doublet treatment strategy to cisplatin-based CCRT in stage II to IVB NPC. ClinicalTrials.gov Identifier: NCT01540136.

Senolytic-Mediated Elimination of Head and Neck Tumor Cells Induced Into Senescence by Cisplatin.

Therapeutic outcomes achieved in head and neck squamous cell carcinoma (HNSCC) patients by concurrent cisplatin-based chemoradiotherapy initially reflect both tumor regression and tumor stasis. However, local and distant metastasis and disease relapse are common in HNSCC patients. In the current work, we demonstrate that cisplatin treatment induces senescence in both p53 wild-type HN30 and p53 mutant HN12 head and neck cancer models. We also show that tumor cells can escape from senescence both in vitro and in vivo. We further establish the effectiveness of the senolytic, ABT-263 (Navitoclax), in elimination of senescent tumor cells after cisplatin treatment. Navitoclax increased apoptosis by 3.3-fold (P ≤ 0.05) at day 7 compared with monotherapy by cisplatin. Additionally, we show that ABT-263 interferes with the interaction between B-cell lymphoma-x large (BCL-XL) and BAX, anti- and pro-apoptotic proteins, respectively, followed by BAX activation, suggesting that ABT-263-induced apoptotic cell death is mediated through BAX. Our in vivo studies also confirm senescence induction in tumor cells by cisplatin, and the promotion of apoptosis coupled with a significant delay of tumor growth after sequential treatment with ABT-263. Sequential treatment with cisplatin followed by ABT-263 extended the humane endpoint to ∼130 days compared with cisplatin alone, where mice survived ∼75 days. These results support the premise that senolytic agents could be used to eliminate residual senescent tumor cells after chemotherapy and thereby potentially delay disease recurrence in head and neck cancer patients. SIGNIFICANCE STATEMENT: Disease recurrence is the most common cause of death in head and neck cancer patients. B-cell lymphoma-x large inhibitors such as ABT-263 (Navitoclax) have the capacity to be used in combination with cisplatin in head and neck cancer patients to eliminate senescent cells and possibly prevent disease relapse.

Impact of cumulative cisplatin dose in childhood nasopharyngeal carcinoma based on neoadjuvant chemotherapy response in the intensity-modulated radiotherapy era: a real-world study

BackgroundWe aimed to comprehensively investigate the optimal cumulative cisplatin dose during concurrent chemoradiotherapy (CC-CCD) for locoregionally advanced nasopharyngeal carcinoma (CA-LANPC) with different tumor responses after neoadjuvant chemotherapy (NAC).MethodsPatients with CA-LANPC who underwent NAC followed by cisplatin-based concurrent chemoradiotherapy were retrospectively analyzed. Evaluation of tumor response in patients was conducted by Response Evaluation Criteria for Solid Tumor (RECIST) 1.1 after two to four cycles NAC. Multivariate Cox proportional hazards models were used for prognosis. Recursive partitioning analysis (RPA) was conducted to classify participates and predict disease-free survival (DFS).ResultsOne hundred and thirty-two patients with favorable response after NAC were included. The median CC-CCD was 163 mg/m2 (IQR, 145–194 mg/m2), and 160 mg/m2 was selected as the cutoff point to group patients into low and high CC-CCD groups (< 160 vs. ≥ 160 mg/m2). There was significant improvement in 5-year DFS (91.2% vs. 72.6%; P = 0.003) for patients receiving high CC-CCD compared to those receiving low CC-CCD. Multivariate analysis revealed that CC-CCD, T stage, and Epstein–Barr virus (EBV) DNA were independent prognostic factors for DFS (P < 0.05 for all). Patients were further categorized into two prognostic groups by RPA: the low-risk group (T1-3 disease with regardless of EBV DNA, and T4 disease with EBV DNA < 4000 copy/mL), and the high-risk group (T4 disease with EBV DNA ≥ 4000 copy/mL). Significant 5-year DFS improvement was observed for the high-risk group (P = 0.004) with high CC-CCD. However, DFS improvement was relatively insignificant in the low-risk group (P = 0.073).ConclusionsCC-CCD was a positive prognostic factor for responders after NAC in CA-LANPC. Furthermore, CC-CCD ≥ 160 mg/m2 could significantly improve DFS in the high-risk group with CA-LANPC, but the benefit of high CC-CCD in the low-risk group needs further study.

Value of 18F-FDG PET/CT for Assessment of Advanced Lacrimal Sac Non-Keratinizing Squamous Cell Carcinoma Successfully Treated with Concurrent Chemoradiotherapy.

Non-keratinizing squamous cell carcinoma (NKSCC) of the lacrimal apparatus is extremely rare. It is usually very aggressive in destroying local tissue and has a grave prognosis for relentless recurrence and distant failures. Though the current evidence cannot make confident recommendations regarding the best management, curative surgical excision with adjuvant radiotherapy remains the most commonly used strategy. Here, we report a 71-year-old woman presented with progressive right medial canthal swellings for six months. A transnasal endoscopic biopsy revealed NKSCC of the lacrimal sac. She then underwent a combination of magnetic resonance images (MRI) and 2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) for staging purposes. Following cisplatin-based concurrent chemo-radiotherapy (CCRT), the post-treatment PET/CT illustrated the absence of an abnormal metabolic accumulation over the suspicious region as observed in post-treatment CT. A further trans-ostia re-biopsy confirmed complete tumor remission. This case demonstrates the remarkable ability of 18F-FDG PET/CT to differentiate between a persistent malignancy and post-treatment changes. Furthermore, a definite CCRT might provide comparable outcomes to traditional surgery.

Efficacy of the pretreatment geriatric nutritional risk index for predicting severe adverse events in patients with head and neck cancer treated with chemoradiotherapy

ObjectiveThe Geriatric Nutritional Risk Index (GNRI) is a simple and well-established nutritional assessment tool. Although concurrent chemoradiotherapy (CCRT), particularly cisplatin-based CCRT, is a standard treatment for locoregional advanced head and neck squamous cell carcinoma (HNSCC), the predictive factors of adverse events related to CCRT remain to be elucidated. The present study aimed to determine the association between GNRI and CCRT-related adverse events in patients of all ages with head and neck cancer (HNC) who underwent CCRT. MethodsWe retrospectively analyzed and compared the clinical characteristics and adverse events of 82 patients with HNC treated with CCRT according to their GNRI at the Department of Otolaryngology, Head and Neck Surgery, University of Tsukuba Hospital, between May 2014 and November 2019. The GNRI was calculated according to the equation: 1.489 × serum albumin (g/L) + 41.7 × (body weight/ideal body weight). We compared two groups: low GNRI (GNRI < 98) and normal GNRI (GNRI ≥ 98) groups. ResultsEighty-two patients were enrolled in this study. There were 61 (76%) and 21 (26%) patients in the normal GNRI group and low GNRI group, respectively. There were significant differences in the incidence of grade ≥ 3 radiation mucositis, radiation dermatitis, and leukopenia between the low GNRI group and the normal GNRI groups. ConclusionsPatients with low GNRI scores were more likely to have severe adverse events. Pretreatment GNRI predicted severe CCRT-related adverse events in patients of all ages with HNC undergoing CCRT.

866P ORCA-2: A phase I study of olaparib in addition to cisplatin-based concurrent chemoradiotherapy for patients with high risk locally advanced (LA) squamous cell carcinoma of the head and neck (HNSCC)

Cisplatin-based chemoradiotherapy (C-CRT) is a standard of care for LA HNSCC, but recurrence is common. Olaparib (PARP-1 inhibitor) inhibits DNA damage and may potentiate anti-tumour activity of C-CRT.

Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy

<h3>Objectives:</h3> The association between the prognosis of advanced cervical cancer treated with cisplatin-based concurrent chemoradiotherapy (CCRT) and the number of tumor-infiltrating lymphocytes (TILs) in biopsy samples collected before treatment was examined, to (i) identify correlations between selected immunogenic factors and clinicopathological characteristics, (ii) determine whether intra-tumoral abundance of various specific TILs is a prognostic indicator in women with advanced cervical cancer who undergo treatment with CCRT, and (iii) investigate subtypes of FOXP3+ T cells in cervical cancer samples. <h3>Methods:</h3> In this retrospective study, intratumoral lesions in colpo-scopic biopsies from 55 women with advanced cervical cancer who subsequently underwent CCRT were analyzed. The informed consent was obtained from all patients, and approval to conduct this study was granted from the institutional review board. The International Federation of Gynecology and Obstetrics clinical stages of these patients were as follows: Stage IIA1 (n=8), Stage IIA2 (n=6), Stage IIb (n=32), Stage IIIa (n=1), and Stage IIIb (n=8). Biopsy samples were subjected to automatic immunological staining using the following six antibodies: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD206, and anti-FOXP3. Associations between the findings on automatic scoring of the number of each type of TIL in each specimen and clinicopathological characteristics or survial status were analyzed. Subtypes of FOXP3+ TILs in 15 additional fresh tumor samples were stained with CD45RA antibody and investigated by flow cytometry. <h3>Results:</h3> Correlations between density of TILs and clinicopathological characteristics were examined. Only weak infiltration of CD8+ lymphocytes was found to be associated with PLN metastasis. No other factors were found to be associated with immune cell infiltration. Better survival was found to be associated with high densities of CD3+, CD4+, CD8+, CD206+, and FOXP3+ T cells, while there were no statistically significant associations with CD20+ B cell density. The subtypes of FOXP3+ TILs were analyzed in 15 fresh tumor samples, and non-Tregs (FOXP3lowCD45RA–) which have anti-tumor activity, were detected in all cases. <h3>Conclusions:</h3> The abundance of various specific intratumoral TILs may be prognostic indicators in patients with advanced cervical cancer undergoing CCRT.

MRI-based radiomics: promise for locally advanced cervical cancer treated with a tailored integrated therapeutic approach

To assess prognostic factors by analyzing clinical and radiomic data of patients with locally advanced cervical cancer (LACC) treated with definitive concurrent cisplatin-based chemoradiotherapy (CCRT) using magnetic resonance imaging (MRI). We analyzed radiomic features from MRI in 60 women with FIGO (International Federation of Gynecology and Obstetrics) stage IB2-IVA cervical cancer who underwent definitive CCRT 45-50.4 Gy (in 25-28 fractions). Thirty-nine (65.0%) received EBRT sequential boost (4-20 Gy) on primary tumor site and 56 (93.3%) received high-dose-rate brachytherapy boost (6-28 Gy) (daily fractions of 5-7 Gy). Moreover, 71.7% of patients received dose-dense neoadjuvant chemotherapy for 6 cycles. The gross tumor volume was defined on T2-weighted sequences and 29 features were extracted from each MRI performed before and after CCRT, using dedicated software, and their prognostic value was correlated with clinical information. In univariate analysis, age ⩾60 years and FIGO stage IB2-IIB had significantly better progression-free survival (PFS) (p = 0.022 and p = 0.009, respectively). There was a trend for significance for worse overall survival (OS) in patients with positive nodes (p = 0.062). In multivariate analysis, only age ⩾60 years and FIGO stage IB2-IIB reached significantly better PFS (p = 0.020 and p = 0.053, respectively). In radiomic dataset, in multivariate analysis, pregray level p75 was significantly associated with PFS (p = 0.047), pre-D3D value with OS (p = 0.049), and preinformation measure of correlation value with local control (p = 0.031). The combination of clinical and radiomics features can provide information to predict behavior and prognosis of LACC and to make more accurate treatment decisions.

Optimal cumulative cisplatin dose during concurrent chemoradiotherapy among children and adolescents with locoregionally advanced nasopharyngeal carcinoma: A real-world data study

PurposeTo identify an optimal cumulative cisplatin dose along with concurrent chemoradiotherapy (CC-CCD) for children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC) using real-world data. Materials and MethodsUsing an NPC-specific database at our center, 157 patients younger than 19 years old with non-disseminated CALANPC and receiving neoadjuvant chemotherapy (NAC) plus cisplatin-based concurrent chemoradiotherapy (CCRT) were enrolled. Confounding factors were controlled by conducting propensity score matching analysis. Primary endpoints include disease-free survival (DFS) and distant metastasis-free survival (DMFS). ResultsThe optimal threshold for CC-CCD with respect to DFS was 160 mg/m2 based on recursive partitioning analyses (RPA). Therefore, a uniform threshold of 160 mg/m2 (≥160 vs. <160 mg/m2) was selected to classify patients between high and low CC-CCD groups for survival analysis. Patients receiving low CC-CCD showed a significant decrease in 5-year DFS (76.6% vs 91.3%; P = 0.006) and DMFS (81.3% vs 93.5%; P = 0.009) compared to those receiving high CC-CCD. Multivariate analyses indicated that high CC-CCD as an favorable prognostic influence for DFS (P = 0.007) and DMFS (P = 0.008). Further matched analysis identified 65 pairs in both high and low CC-CCD groups. In the matched cohort, high CC-CCD was still identified as a favorable factor for prognosis in DFS (HR, 0.23; 95% CI, 0.08–0.70; P = 0.010) and DMFS (HR, 0.23; 95% CI, 0.06–0.82; P = 0.023). ConclusionCC-CCD exerts significant treatment effects and 160 mg/m2 CC-CCD may be adequate to provide antitumor effects for CALANPC receiving NAC plus CCRT.

A randomized phase II trial of diffusion-weighted MR imaging-guided radiotherapy plus chemotherapy versus standard chemoradiotherapy in locoregional advanced nasopharyngeal carcinoma.

6018 Background: We hypothesized that diffusion-weighted MR imaging (DWI) guided dose-painting radiotherapy (DP-RT) was associated with improved tumor control and survival compared with standard CT-based radiotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). The purpose of this randomized phase II trial was to compare the efficacy and toxicity of DWI guided DP-RT plus chemotherapy versus standard CT-based radiotherapy plus chemotherapy in locoregionally advanced NPC. Methods: Two hundred and fifty-six patients with stage III-IVa (8th AJCC) NPC were randomly assigned to receive DWI-guided dose-painting radiotherapy plus chemotherapy (DP-RT group, n = 128) or standard CT-based radiotherapy plus chemotherapy (CT-based RT group, n = 128). Patients in both groups received 3 cycles of induction chemotherapy followed by cisplatin-based concurrent chemoradiotherapy. In DP-RT group, subvolume GTVnx-DWI (gross tumor volume of nasopharynx in DWI) was defined as the areas within the GTVnx (gross tumor volume of nasopharynx) with an apparent diffusion coefficient (ADC) below the mean ADC (ADC &lt; mean). The dose to GTVnx-DWI was escalated to DT 75.2 Gy/32 Fx in patients with T1-2 disease, and DT 77.55 Gy/33 Fx in those with T3-4 disease, in 2.35 Gy per fraction. In CT-based RT group (n = 128), PGTVnx was irradiated at DT 70.4-72.6 Gy/32-33 Fx in 2.2 Gy per fraction. This trial is registered with chictr.org.cn, number ChiCTR1800015779. Results: Compared with standard CT-based radiotherapy, DWI-guided DP-RT significantly improved 2-year local recurrence-free survival (LRFS, 100% vs. 95.4%; P = 0.024), distant metastasis-free survival (DMFS, 97.9% vs. 90.6%; P = 0.006), disease free survival (DFS, 93.2% vs. 86.8%; P = 0.021), and overall survival (OS, 100% vs. 95.2%; P = 0.038). No statistically significant differences in acute and late toxic effects were observed. Multivariate analysis showed that dose painting (DWI-guided DP-RT vs CT-based RT without DP) was a significant independent prognostic factor for DMFS and DFS (P = 0.021 and P = 0.020, respectively). Conclusions: Diffusion-weighted MR imaging guided dose-painting radiotherapy plus chemotherapy is associated with a considerable survival benefit, without increasing toxicity, as compared with standard CT-based radiotherapy plus chemotherapy, among patients with locoregionally advanced nasopharyngeal carcinoma. Clinical trial information: ChiCTR1800015779.

OROPHARYNGEAL SQUAMOUS CELL CARCINOMA TREATED CONCURRENTLY WITH CETUXIMAB: A CASE REPORT OF INTOLERANCE TO CISPLATIN IN YOUNG AGE

Squamous cell carcinoma of the oropharynx is a common case of head and neck cancer related to human papillomavirus. We present a case of moderately (G2) differentiated squamous cell carcinoma, which responded well to concurrent radiotherapy with cetuximab after intolerance of cisplatin. A 37-year-old woman referred to our hospital for a locally advanced cancer of the base of tongue. Physical examination revealed an ulcerative tumor with spread to the supraglottic structures, and swelling of the right side cervical lymph node at group IIA. The histological diagnosis from a biopsy specimen was moderately differentiated p16 positive squamous cell carcinoma. The patient underwent cisplatin-based concurrent chemoradiotherapy. Two – three weeks after receiving an intravenous cisplatin dose 100 mg/m 2 for the first day of chemorradiation, the patient presented with profound bilateral sensorineural hearing loss. The cisplatin-based chemotherapy had changed to alternative agent. The patient continuously underwent concurrently radiation with cetuximab without the break of radical radiotherapy course. The patient experienced partial recovery of hearing after radical treatment of cancer. Complete clinical and radiological response of oropharyngeal squamous carcinoma was achieved. Conclusions. Toxicity with only one standard dose of cisplatin can be profound also in young age. This risk should be addressed when counseling patient prior to initiation of treatment. In case of platinum ineligibility, replacing cisplatin with less toxic agent cetuximab may be taken into consideration for p16 positive carcinoma of the oropharynx.

Weekly versus triweekly cisplatin-based concurrent chemoradiotherapy for nasopharyngeal carcinoma: a systematic review and pooled analysis.

Background: Weekly and triweekly cisplatin-based concurrent chemoradiotherapy (CCRT) have been used in the treatment of nasopharyngeal carcinoma (NPC).Objective: This study aimed to compare the benefits and risks between the two treatments.Methods: We systematically searched electronic databases for prospective and retrospective clinical studies of NPC patients who received weekly compared with triweekly cisplatin-based CCRT. The primary endpoints comprised overall, failure-free, distant metastasis-free, and locoregional recurrence-free survivals (OS, FFS, DMFS, and LRFS). Secondary endpoints were toxicities.Results: Six studies were included in the systematic review, of which four with 1515 NPC patients were eligible for further pooled analysis. There were no significant differences between weekly and triweekly groups in terms of 5-year OS (odds ratio [OR] 0.95, 95% confidence interval [CI] 0.51-1.79), FFS (OR 1.09, 95% CI 0.67-1.76), DMFS (OR 1.25, 95% CI 0.54-2.92), and LRFS (OR 0.83, 95% CI 0.55-1.25). For grade ≥ 3 toxicities, the weekly group had higher risks of anemia (risk ratio [RR] 2.96, 95% CI 1.12-7.81) and thrombocytopenia (RR 2.75, 95% CI 1.54-4.90), but a lower incidence of vomiting (RR 0.34, 95% CI 0.18-0.63) versus the triweekly group.Conclusion and Relevance: Both weekly and triweekly schedules could be recommended to NPC patients during CCRT. Additionally, hematologic adverse events in weekly strategy and non-hematologic adverse events in triweekly strategy are of higher concern.

280P Safety and efficacy of concurrent chemoradiotherapy for head and neck cancers in younger versus older patients: Post hoc analysis of a randomized control trial

Head and neck squamous cell carcinoma (HNSCC) is a well-known malignancy in the older population. However, there is scarcity of data on the effect of chemoradiation on them. We did a posthoc analysis of a randomized study conducted at our institution to understand this effect. We did a posthoc analysis of the study where the patients received chemoradiation. The database of this study was used for the present analysis. We evaluated the differences in demography, grade 3 or worse adverse events, compliance of treatment, loco-regional control (LRC), progression free survival (PFS) and overall survival (OS) between older (≥ 60 years) and the younger patients. Out of 300 patients, 283 (94.3%) comprised the younger cohort (age < 60 years) while the older cohort included 17 (5.7%) patients. There was no difference in the occurrence of severe (grade 3/4) toxicities in the older cohort when compared to the younger patients. At a median follow up period of 22 months (range, 3-51), the cumulative LRC at 2 years was 67.1% and 100% in younger and the older group respectively (P = 0.018). The estimated median PFS in younger patients was 24.4 months (95% CI, 12.5 to 36.3), while it was not reached in the older group (P = 0.53). The estimated median OS was 41.3 months in the younger and not reached in the older group (P = 0.613). Older patients with locally advanced HNSCC who received radical concurrent cisplatin-based chemoradiotherapy showed significantly better LRC. Older patients experienced similar adverse events as compared to the younger ones.

Tumor-infiltrating lymphocytes predict survival outcomes in patients with cervical cancer treated with concurrent chemoradiotherapy

ObjectivesTo (i) identify correlations between selected immunogenic factors and clinicopathological characteristics, (ii) determine whether intratumoral abundance of various specific tumor-infiltrating lymphocytes (TILs) is a prognostic indicator in women with Stage II and III cervical cancer who undergo treatment with cisplatin-based concurrent chemoradiotherapy (CCRT), and (iii) investigate subtypes of FOXP3+ T cells in 15 fresh samples of cervical cancer. MethodsIn this retrospective study, intratumoral lesions in colposcopic biopsies from 55 women with advanced cervical cancer who subsequently underwent CCRT at our institution were subjected to automatic immunological staining using the following six mouse monoclonal antibodies: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD206, and anti-FOXP3. Associations between the findings on automatic scoring of the number of each type of TIL in each specimen and various clinicopathological characteristics were analyzed, as were associations between the abundance of various specific types of TIL and survival. Subtypes of FOXP3+ TILs in 15 additional fresh tumor samples were also investigated using flow cytometry. ResultsInfiltration with CD8+ TILs was associated with pelvic lymph node metastasis. Abundant infiltration by CD3+, CD4+, CD8+, CD206+, and FOXP3+ TILs were statistically significant indicators of better progression-free and overall survival. Regarding subtypes of FOXP3+ TILs, non-Tregs (Fr-III) were found in all samples tested for this. ConclusionsThe abundance of various specific intratumoral TILs may be prognostic indicators in patients with advanced cervical cancer undergoing CCRT.

The evaluation of adding induction chemotherapy to concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma: a meta-analysis.

We performed a meta-analysis to compare the efficacy and safety of induction chemotherapy (IC) followed by cisplatin-based concurrent chemoradiotherapy (CCRT) versus cisplatin-based CCRT for patients with locally advanced nasopharyngeal carcinoma (LA-NPC). We systematically searched PubMed, the Cochrane Library and Embase until February 29, 2020, for eligible randomized controlled trials (RCTs). The quality of the studies was assessed with the Cochrane Collaboration risk of bias tool. The following outcomes of interest were analyzed: 1) progression-free survival (PFS); 2) overall survival (OS); 3) distant metastasis-free survival (DMFS); 4) locoregional failure-free survival (LRFFS); and 5) any grade 3 or 4 treatment-related adverse events (AEs). The data were pooled with the use of hazard ratios (HRs) or odds ratios (ORs). Subgroup, heterogeneity and sensitivity analyses were performed. After screening all studies selected from the initial search, seven trials with 2233 patients met the inclusion criteria. Compared to cisplatin-based CCRT alone, there was reliable evidence that IC significantly improved PFS (HR 0.65, 95% CI 0.55-0.75, P < 0.00001), OS (HR 0.61, 95% CI 0.45-0.83, P = 0.002), DMFS (HR 0.65, 95% CI 0.53-0.79, P < 0.0001) and LRFFS (HR 0.68, 95% CI 0.53-0.88, P = 0.003) and was associated with a markedly increased risk of AEs (grade 3/4) during the IC and CCRT phases. No significant difference in the incidence of late AEs (grade 3/4) was observed between different arms. Compared to cisplatin-based CCRT alone, IC followed by cisplatin-based CCRT confers real and substantial favorable survival outcomes with controllable toxicities. Therefore, it is reasonable to define IC followed by cisplatin-based CCRT as one of the standard treatment strategies for patients with LA-NPC.

Effect of BRCA1 on the Concurrent Chemoradiotherapy Resistance of Cervical Squamous Cell Carcinoma Based on Transcriptome Sequencing Analysis.

Background Cervical squamous cell carcinoma (CSCC) is the main pathological type of cervical cancer, accounting for 80%–85% of cervical cancer. Owing to concurrent chemoradiotherapy (CCRT) resistance in a subset of CSCC patients, the treatment response is often unsatisfactory. Identifying predictors and therapeutic targets related to cisplatin-based CCRT resistance in CSCC is critical. Methods We reanalyzed GSE56363, an mRNA dataset from the GEO database with 21 patients with locally advanced CSCC, to identify differentially expressed genes (DEGs) related to CCRT resistance. The hub genes were screened from the protein-protein interaction network of DEGs using cytoHubba plug-in of Cytoscape software. Transcriptome sequencing technology was used to compare differential expression between SiHa cells overexpressing BRCA1 compared with control SiHa cells. Functional annotation for DEGs and gene set enrichment analysis (GSEA) was performed to identify DEG-enriched relative signaling pathways to examine the molecular mechanisms of BRCA1 in CCRT resistance of CSCC. qPCR was used to verify the expression of key genes in SiHa/DDP cells. Results A total of 609 DEGs including 223 upregulated DEGs and 386 downregulated DEGs were identified between the complete response to CCRT (CR) and noncomplete response to CCRT (NCR) CSCC patients based on the GSE56363 dataset. Ten hub genes with the highest degrees were identified via the plug-in CytoHubba in Cytoscape: BRCA1, CDCA8, ASPM, CDC45, RAD51, HMMR, CENPF, EXO1, DTL, and ZWINT genes, and BRCA1 ranked first. Through transcriptome sequencing analysis based on GSE141558, 1344 DEGs were identified in BRCA1-overexpressing SiHa cells, including 824 upregulated DEGs and 520 downregulated DEGs. GSEA results showed that CCRT-resistance related signaling pathways, such as the JAK/STAT signaling pathway and the WNT signaling pathway, were differentially enriched in BRCA1-expressing SiHa cells. STAT1, STAT2, and CCND1 were screened as the differentially expressed target genes of BRCA1 and may correlate with resistance of CSCC. qPCR results showed that only STAT1 was significantly increased in SiHa cells with GV230-BRCA1 plasmid transfection. Conclusion BRCA1 overexpression in SiHa cells may upregulate STAT1 to activate the JAK/STAT signaling pathway, suggesting a mechanism for enhanced CCRT resistance.

Neoadjuvant chemotherapy followed by radical surgery versus concurrent chemoradiotherapy in patients with FIGO stage IIB cervical cancer: the CSEM 006 study

BackgroundConcurrent chemoradiotherapy is the first-line treatment for FIGO stage IIB cervical cancer. Neoadjuvant chemotherapy followed by radical surgery may provide another treatment option.Primary objectiveTo compare the therapeutic outcomes of neoadjuvant...

Efficacy and tolerability of weekly 40mg/m² cisplatin radiosensitizing modified regimen for locally-advanced head and neck squamous cell carcinoma radical treatment with chemoradiotherapy: A university hospital experience.

e18512 Background: Cisplatin-based chemoradiotherapy (CRT) is a well-established regimen used for adjuvant and/or head-and-neck squamous cell carcinoma (HNSCC) radical treatment. The most classic protocol for chemoradiotherapy remains the administration of Cisplatin 100mg/m² EV D1 q3-week period, 3 cycles. The objective of this study is to assess the efficacy and tolerability of the weekly 40mg/m² cisplatin regimen. Methods: we conducted a retrospective study from 2007-2020 with 102 patients treated at a national reference institution. All of them with HNSCC received concurrent CRT with weekly cisplatin 40mg/m² EV D1. We analyzed the overall survival (OS), local recurrence and tolerability in this scheme. Results: The median cisplatin cumulative dose received by our patients was 240mg/m². Hence, we divided them in two groups for the analysis: Group A (41 patients) received less than 240mg/m² cisplatin total dose and Group B (61 patients) received more or equal 240mg/m² cisplatin total dose. Both groups were equally balanced between sex, clinic stage, histologic grade and clinic status. We found that the Group A experienced 5 deaths (12.2%) while the Group B experienced 6 deaths (9.8%). The mean time to recurrence disease in the Group A was 45.68 months and in Group B 60.22 months (p = 0.958). The estimated overall survival in the Group A was 150 months and in the Group B was 116.4 months (p = 0.443). Conclusions: The weekly cisplatin dose regimen showed to be feasible, more tolerable, and less toxic and with no difference in terms of OS then the classic 3-week cisplatin protocol in the CRT setting. Our group suggests that the 240mg/m² cumulative cisplatin weekly schedule should be a better option for CRT treatments then the classic cisplatin regimen. A phase III clinical trial is warranted to further understanding of this framework. Key-words: head and neck cancer, cisplatin, radiotherapy