Cisplatin Chemoradiotherapy Research Articles

The role of genetic variants in the prediction of hearing loss due to cisplatin chemoradiotherapy.

Concomitant high-dose cisplatin with radiotherapy is commonly used for treating head and neck squamous cell carcinoma (HNSCC). Cisplatin, often used with radiotherapy, is known for causing irreversible sensorineural hearing loss, with individual variability suggesting a genetic component. This study aims to enhance the predictive ability of the clinical prediction model for cisplatin-induced hearing loss (CIHL) in HNSCC patients, as outlined in Theunissen etal., by incorporating significant genetic variants. Conducted at the Netherlands Cancer Institute, this retrospective study included 74 patients treated between 1997 and 2011. Thirty-one SNPs that were previously associated with CIHL or other cisplatin-induced toxicities were identified and incorporated into the model. The primary outcome measured was the change in decibels at posttreatment 1-2-4 kHz hearing levels per additional minor allele of these SNPs, evaluated using linear mixed-effects regression models. The model's predictive accuracy was determined by the area under the curve (AUC) using 10-fold cross-validation. The rs2289669 SNP in the SLC47A1/MATE1 gene was linked to a significant 2.67 dB increase in hearing loss per allele (95% CI 0.49-4.86, p = 0.017). Incorporating rs2289669 improved the model's AUC from 0.78 to 0.83, a borderline significant improvement (p = 0.073). This study underscores the importance of the rs2289669 SNP in CIHL and demonstrates the potential of combining genetic and clinical data for enhanced predictive models in personalized treatment strategies.

Nonpersistent Nanoarchitectures Enhance Concurrent Chemoradiotherapy in an Immunocompetent Orthotopic Model of HPV+ Head/Neck Carcinoma.

Cisplatin chemoradiotherapy (CRT) is the established standard of care for managing locally advanced human papillomavirus-positive head/neck carcinoma. The typically young patients may suffer serious and long-time side effects caused by the treatment, such as dysphagia, and hearing loss. Thus, ensuring a satisfactory post-treatment quality of life is paramount. One potential replacing approach to the classical CRT involves the combination of standard-dose radiotherapy and radiosensitizers such as noble metal nanoparticles (NPs). However, several concerns about size, shape, and biocompatibility limit the translation of metal nanomaterials to the clinical practice. Here, it is demonstrated that a new model of nonpersistent gold nanoarchitectures containing cisplatin (NAs-Cluster-CisPt) generates, in combination with radiotherapy, a significant in vivo tumor-reducing effect compared to the standard CRT, achieving a complete tumor clearance in 25% of the immunocompetent models that persist for 60 days. These findings, together with the negligible amount of metals recognized in the excretory organs, highlight that the concurrent administration of NAs-Cluster-CisPt and radiotherapy has the potential to overcome some clinical limitations associated to NP-based approaches while enhancing the treatment outcome with respect to standard CRT. Overall, despite further mechanistic investigations being essential, these data support the exploiting of nonpersistent metal-nanomaterial-mediated approaches for oral cancer management.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer

BackgroundEvaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC).MethodsRetrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs).ResultsA total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314–0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343–0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05).ConclusionsIn LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

MiR-6805-5p as a biomarker of cisplatin-induced nephrotoxicity in patients with head and neck cancer

Introduction: The standard treatment for head and neck squamous cell carcinoma (HNSCC) is cisplatin chemoradiotherapy. One of the main treatment adverse reactions is nephrotoxicity, for which there is currently no adequate specific and sensitive biomarker. Thus, this study aimed to evaluate the use of microRNAs (miRNAs) as renal biomarker candidates.Methods: This was a retrospective cohort study. Nephrotoxicity was assessed through blood samples collected before and 5 days (D5) after chemotherapy. MiRNAs were extracted from urine samples collected at baseline and D5, and RNA sequencing identified miRNAs differentially expressed between participants with and without cisplatin-induced nephrotoxicity.Results: A total of 49 participants were included (n = 49). A significant difference was seen between the two groups for traditional renal markers (serum creatinine and creatinine clearance) and for the acute kidney injury (AKI) categories. Among the six miRNAs evaluated as biomarkers, four were upregulated (hsa-miR-6729-5p, hsa-miR-1238-5p, hsa-miR-4706, and hsa-miR-4322) and two were downregulated (hsa-miR-6805-5p and hsa-miR-21-5p), but only hsa-miR-6805-5p had a significant difference (p < 0.0001). Its receiver operating characteristic curve revealed excellent specificity (0.920) for its expression fluctuation assessment, while its absolute expression in D5 showed greater sensitivity (0.792).Conclusion: So, the integrated use of these two parameters seems to be an interesting approach for AKI.

Data Normalization of Urine miRNA Profiling from Head and Neck Cancer Patients Treated with Cisplatin.

The microRNA (miRNA) expression profile by qRT-PCR depends directly on the most appropriate normalization strategy adopted; however, currently there is no universally adequate reference gene. Therefore, this study aimed to determine, considering RNA-Seq results, the most adequate endogenous normalizer for use in the relative quantification of urine miRNAs from head and neck cancer patients, treated with cisplatin chemoradiotherapy. The massive sequencing was performed to identify the miRNAs differentially expressed between the group with cisplatin nephrotoxicity (n = 6) and the one without (n = 6). The candidate endogen normalizer was chosen according to four criteria: (1) the miRNA must be expressed in most samples; (2) the miRNA must have a fold change value between 0.99 and 1.01; (3) the miRNA must have a p-value ≥ 0.98; and (4) the miRNA must not be commented on by the final GeneGlobe (Qiagen, Hilden, Germany) analysis. Four miRNAs met all the criteria (hsa-miR-363-5p, hsa-miR-875-5p, hsa-miR-4302, and hsa-miR-6749-5p) and were selected for validation by qRT-PCR in a cohort of 49 patients (including the 12 sequencing participants). Only hsa-miR-875-5p was shown to be an adequate normalizer for the experimental condition under investigation, as it exhibited invariant expression between the two groups.

Weekly versus 3-weekly cisplatin along with radiotherapy for locoregionally advanced non-nasopharyngeal head and neck cancers: Is the equipoise in literature addressed yet?

Concurrent chemoradiotherapy with 3-weekly cisplatin 100 mg/m2 has been the standard of care for locoregionally advanced head and neck cancer (LA-HNC) with level I evidence. While the outcomes in terms of efficacy have been well established, the toxicity profile, compliance, and real-world applicability has been an area of ongoing concern for this regimen, leading the oncologists to explore weekly cisplatin chemoradiotherapy regimen to potentially address the issue. A review of literature was conducted in Pubmed, Scopus, and Medline to compare and evaluate the present role of weekly cisplatin chemotherapy along with radiotherapy versus 3-weekly cisplatin chemotherapy along with radiotherapy in both adjuvant and definitive settings for locoregionally advanced head and neck cancers. Nasopharyngeal subsites were excluded from the literature review and 50 relevant articles were included in the analysis. Recently published evidences of noninferiority of weekly over 3-weekly cisplatin chemoradiotherapy regimen in definitive as well as adjuvant settings in locoregionally advanced head and neck cancers is highlighted and interpreted. Results supporting and against the above in different publications is elaborated in this article. Trials designed to demonstrate noninferiority of the weekly cisplatin chemoradiotherapy regimen over 3-weekly regimen, especially in definitive setting may conclude the debate in future. A lacunae in the existing literature is noted in the form of lack of superiority trials on the above topic, which may impact future conclusions.

Low skeletal muscle mass is predictive of dose-limiting toxicities in head and neck cancer patients undergoing low-dose weekly cisplatin chemoradiotherapy.

The dose-limiting effect of CT-assessed low skeletal muscle mass (LSMM) measured at the level of the third cervical vertebra has been found in head and neck cancer patients receiving high-dose cisplatin chemoradiotherapy. The aim of this study was to investigate the predictive factors for dose-limiting toxicities (DLTs) using low-dose weekly chemoradiotherapy. Head and neck cancer patients receiving definite chemoradiotherapy with weekly 40 mg/m2 body surface area (BSA) cisplatin or paclitaxel 45 mg/m2 BSA and carboplatin AUC2 were consecutively included and retrospectively analysed. Skeletal muscle mass was assessed using the muscle surface at the level of the third cervical vertebra in pretherapeutic CT scans. After stratification for LSMM DLT, acute toxicities and feeding status during the treatment were examined. Dose-limiting toxicity was significantly higher in patients with LSMM receiving cisplatin weekly chemoradiotherapy. For paclitaxel/carboplatin, no significance regarding DLT and LSMM could be found. Patients with LSMM had significantly more dysphagia before treatment, although feeding tube placement before treatment was equal in patients with and without LSMM. LSMM is a predictive factor for DLT in head and neck patients treated with low-dose weekly chemoradiotherapy with cisplatin. For paclitaxel/carboplatin, further research must be carried out.

Abstract 3443: The IAP antagonist xevinapant, in combination with high-dose cisplatin chemoradiotherapy, induces NF-kB and apoptotic pathway biomarkers in patients with high-risk locally advanced squamous cell carcinoma of the head and neck

Abstract Introduction: Inhibitor of Apoptosis Proteins (IAPs) regulate apoptosis and modulate NF-kB signaling, which in turn drives the expression of genes involved in immune and inflammatory responses. Xevinapant (XVT) (a.k.a Debio 1143) is an orally available IAP antagonist shown to enhance tumor response to radiation through the proapoptotic cytokine TNFα and caspase activation. Results from a double-blind, multicenter, randomized, phase II trial in patients with high-risk locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN) revealed significant improvement in overall survival (OS), progression free survival (PFS) and duration of response with XVT in combination with high-dose cisplatin chemoradiotherapy (CRT) vs CRT alone (NCT02022098). We analyzed XVT pharmacodynamic (PD) biomarker time-concentration profiles and explored the association of PD changes over time with clinical efficacy and safety parameters. Methods: Three serum PD biomarkers were measured during cycle 1: caspase-cleaved cytokeratin 18 fragment (CKM30), a biomarker of epithelial apoptosis, MCP1 and TNFα, both NF-kB target genes. Time course changes in PD biomarker exposure, measured by their Area Under the Curve (AUC), were tested for association with clinical efficacy and safety endpoints, by linear, logistic, and Cox Proportional Hazard models. Clinical response parameters included locoregional control (LRC) at 18 months from end of treatment (EOT), PFS, duration of LRC, time to distant relapse (TTDR), OS and complete response (CR) 6 months after EOT. Results: The biomarker analysis set was composed of all patients with baseline PD assessments and at least one post-baseline measurement and included 35 and 40 patients in the XVT and placebo (PBO) arms, respectively. All three serum PD biomarkers increased upon administration of CRT + XVT during cycle 1. The increase in CKM30 and MCP1 levels was significantly higher in the CRT + XVT arm vs the CRT + PBO arm, as tested by linear mixed effect models (CKM30: p = 0.0167; MCP1: p = 0.0135). Interestingly, CKM30 AUC appeared to be correlated with response in CRT + XVT but not CRT + PBO (based on LRC at month 18 or CR at month 6). No associations between any of the three biomarkers were observed with the safety endpoints explored. Conclusions: Xevinapant has demonstrated promising activity in combination with CRT in LA-SCCHN. The outcome of the exploratory PD analyses indicates that XVT modulates NF-kB signaling, leading to serum increases in MCP1 and TNFα while further augmenting CRT-induced apoptotic marker CKM30. Our findings further characterize the mechanism of action of XVT and how it may ultimately result in enhanced clinical responses to CRT. Citation Format: Luke Piggott, Bruno Gavillet, Franck Brichory, Kathrin Gollmer, Florilene Bouisset, Gregoire Vuagniaux. The IAP antagonist xevinapant, in combination with high-dose cisplatin chemoradiotherapy, induces NF-kB and apoptotic pathway biomarkers in patients with high-risk locally advanced squamous cell carcinoma of the head and neck [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3443.

Survival and toxicity of weekly cisplatin chemoradiotherapy versus three-weekly cisplatin chemoradiotherapy for head and neck cancer: A systematic review and meta-analysis endorsed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO).

To evaluate efficacy and toxicity of weekly cisplatin chemoradiotherapy versus three-weekly cisplatin chemoradiotherapy and identify differences in clinical outcomes and severe toxicity rate. PICOS/PRISMA methods were used to identify studies on PubMed, EMBASE and Cochrane Library, 2005-2019. Six randomized clinical trials (554 patients) were identified. Weekly cisplatin was not associated with significant overall survival (HR 1.13, 95 % CI 0.84-1.51) and progression-free survival (HR 1.23, 95 %CI 0.91-1.65) improvement compared with three-weekly regimen. Severe acute toxicity (RR 0.95), treatment compliance to chemotherapy (RR 1.67) and radiotherapy (RR 0.61) were similar between regimens. Weekly cisplatin is not associated with better clinical outcomes compared to three-weekly cisplatin. Three-weekly cisplatin chemoradiotherapy should be considered the standard approach in the management of locally advanced head and neck cancer. Methodologically robust RCTs designs are needed to improve the quality of evidence. Differences on long-term toxicity and cost-effectiveness remain to be tested.

Superselective intra-arterial chemoradiotherapy using altered blood flow compared to conventional systemic chemoradiotherapy for locally advanced oral squamous cell carcinoma: a single-center retrospective study.

To evaluate the efficacy and safety of superselective intra-arterial (IA) chemoradiotherapy with cisplatin and transcatheter arterial embolization (TAE) on advanced oral cancer, and to compare it with that of systemic chemoradiotherapy. This single-center retrospective study included 23 consecutive patients with locally advanced oral squamous cell carcinoma from November 2011 to November 2019. Of these, 15 received superselective IA cisplatin chemoradiotherapy with altered blood flow in the branches of the external carotid artery, and eight received systemic chemoradiotherapy. Medical charts were reviewed for the evaluation of patient data, drug toxicity, and antitumor efficacy. Local control rate for the superselective IA infusion group, who underwent 6-7 cycles was significantly higher than that of the systemic chemotherapy group (11/13, 85% vs 3/8, 38%; p = 0.04). Regional control, locoregional control, disease-free survival, and overall survival rates were not significantly different between the groups (p = 0.15-0.907). Acute toxicity rates of grade 3 or higher were not significantly different between the IA and IV chemotherapy groups (p = 0.221). Superselective IA chemoradiotherapy with cisplatin using altered blood flow in the branches of the external carotid artery with TAE may be useful for inoperable oral cancer.

Phase II study of pembrolizumab after chemoradiotherapy (CRT) as adjuvant therapy for locally advanced esophageal squamous cell carcinoma (LA-ESCC) patients at high risk of recurrence following preoperative CRT plus surgery.

TPS259 Background: LA-ESCC is a potentially curable disease, for which preoperative CRT followed by esophagectomy is a standard-of-care. Previous studies have identified that close/involved margin and lymph node metastasis with extranodal invasion (ENI) in post-CRT surgical specimens are associated with increased risk of recurrence. In CheckMate-577 trial, adjuvant nivolumab significantly improved disease-free survival (DFS) in patients with esophageal cancer treated with preoperative CRT and surgery; in another trial (the “PACIFIC” trial), adjuvant durvalumab has significantly improved overall survival (OS) in stage III non-small cell lung cancer treated with definitive CRT. We hypothesize that adding pembrolizumab to CRT as an adjuvant therapy would improve the outcomes of LA-ESCC patients who are treated with preoperative CRT plus esophagectomy and with high-risk of recurrence. Methods: This single institution single-arm phase II study include patients with histologically confirmed LA-ESCC (AJCC 7th staging system:cT3-4aN0M0 or T1-4aN1-3M0) harboring at least one risk factor (closed/involved margin, ENI, or ypN2-3) in post-CRT surgical specimens. Patients with adenocarcinoma of esophagus or gastroesophageal junction or synchronously diagnosed with a squamous cell carcinoma of aero-digestive way other than ESCC are excluded. Patients enrolled will receive adjuvant weekly cisplatin–CRT (cisplatin, 30mg/m2 for 2 cycles every week; radiotherapy, 180-200 cGy/fraction for 10-13 times) followed by pembrolizumab (200 mg, every 3 weeks, for 18 cycles). The primary endpoint of this study is 1-year relapse-free survival (RFS) rate; and the key secondary endpoints include RFS, 3-year RFS rate, OS, 3-yr OS rate, toxicity and safety. The study, registered with clinical trial ID of NCT03322267, started patient enrollment in Aug 2018. As of Aug of 2020, 11 of 46 planned patients have been enrolled. Clinical trial information: NCT03322267.

Chemoradiotherapy plus a SMAC mimetic for locally advanced squamous cell carcinoma of the head and neck

The availability of checkpoint inhibitors has led to substantial progress in the treatment of patients with recurrent or metastatic squamous cell carcinoma of the head and neck. For locoregionally advanced disease, a potentially curable condition, concomitant chemotherapy and radiotherapy (chemoradiotherapy) has remained the mainstay of organ-sparing treatment. However, the treatment outcome of locoregionally advanced squamous cell carcinoma of the head and neck, traditionally associated with alcohol and nicotine consumption, still remains poor. A notable exception is human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma, which represents a distinct disease entity with a more favourable prognosis. Although various regimens are used in daily clinical practice, high-dose cisplatin chemoradiotherapy is considered to be the standard of care and the most effective chemoradiotherapy regimen in terms of oncological outcome. In this regard, HPV-positive locoregionally advanced oropharyngeal squamous cell carcinoma is no exception, as was recently demonstrated in two randomised trials. 1 Oosthuizen JC Doody J De-intensified treatment in human papillomavirus-positive oropharyngeal cancer. Lancet. 2019; 393: 5-7 Summary Full Text Full Text PDF PubMed Scopus (12) Google Scholar Serious treatment-related toxicity resulting from high-dose cisplatin chemoradiotherapy, both acute and chronic, is common, and appropriate patient selection for this treatment is crucial. Additionally, disease recurrence following chemoradiotherapy is prevalent, especially for patients with high-risk HPV-negative squamous cell carcinoma of the head and neck. Upon relapse, prognosis is generally poor because salvage treatment options are often scarce. Therefore, the need for more effective treatment regimens remains. Debio 1143 and high-dose cisplatin chemoradiotherapy in high-risk locoregionally advanced squamous cell carcinoma of the head and neck: a double-blind, multicentre, randomised, phase 2 studyTo our knowledge, this is the first treatment regimen to achieve superior efficacy in this disease setting against a high-dose cisplatin chemoradiotherapy comparator in a randomised trial. These findings suggest that inhibition of inhibitor of apoptosis proteins is a novel and promising approach in this poor prognostic population and warrant confirmation in a phase 3 study with the aim of expanding the therapeutic options for these patients. Full-Text PDF

Routine feasibility of postoperative chemoradiotherapy in head and neck squamous cell carcinoma at high risk of recurrence

ObjectiveTo assess the feasibility in routine practice of postoperative chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC) at high risk of recurrence. MethodA single-center retrospective study recruited all patients receiving postoperative cisplatin chemoradiotherapy for HNSCC at high risk of recurrence. The main endpoints were the rate of complete postoperative chemoradiotherapy and the impact of various clinical factors. Secondary endpoints comprised the impact of completion of therapy on survival and on acute and late toxicity. ResultsOne hundred and six patients were included. 24.5% showed severe comorbidity. Chemoradiotherapy was complete in 61 patients (57.5%). Radiation therapy was interrupted for >3 days in 16 patients (15.1%). The 3rd concomitant cisplatin course could not be implemented in 34 patients (32.1%). Low pre-treatment glomerular filtration rate was significantly associated (p=0.003) with treatment interruption; >5% weight-loss during treatment showed suggestive association (p=0.026). Completion of treatment was not associated with any significant difference in overall survival (p=0.441) or progression-free survival (p=0.81). 14.9% of patients showed post-treatment kidney failure; there were 10 cases of osteoradionecrosis (9.4%). ConclusionThe rate of complete postoperative chemoradiotherapy was comparable to that reported in clinical trials, despite frequent comorbidity and poor nutritional status. Early nutritional support is a key factor for treatment under optimal conditions.

1158P - Blood-based testing of mutations in patients with head and neck squamous cell carcinoma (HNSCC) using highly sensitive SafeSEQ technology

BackgroundTumour molecular profiling in HNSCC is not routinely incorporated into clinical practice due to lack of validated biomarkers. Liquid biopsy represents noninvasive approach to capture tumour heterogeneity and evolution during treatment. We utilized highly sensitive sequencing method, SafeSEQ, to evaluate plasma circulating tumour DNA (ctDNA) in 2 cohorts of HNSCC patients (pts) with locally advanced (LA) and metastatic disease. MethodsCohort 1 included 54 pts with LA HNSCC treated with cisplatin chemoradiotherapy. Plasma was obtained at baseline, end of treatment (EOT) and disease progression (PD) and compared to baseline tissue mutation status. Cohort 2 included 15 pts with metastatic disease who received nivolumab, plasma results were compared at baseline and post 2ndcycle. Sequencing for p53, CDKN2A, HRAS and PIK3CA was performed with SafeSEQ on both plasma and tissue specimens. Results51/54 pts with LA disease were evaluated at baseline for tissue (t) and plasma (p) mutation status. P53 was the most common mutation (t: 49%), p: 39%) followed by CDKN2A (t: 17.6%,p: 4%), PIK3CA (t: 9.8%, p: 6%) and HRAS (t: 7.8%, p: 4%). Interestingly 3 (5.8%) pts had detectable HRAS mutations in plasma that were not detected in tissue at baseline. In LA pts whose tumor harbored mutation, ctDNA was detectable in 56% at baseline. Concordance of mutation results between baseline plasma and tissue was 51%. At PD (N=10) ctDNA exhibited higher rate of detectability compared to baseline and novel mutations emerged in 40% of cases. In cohort 2, 93% (14/15) of metastatic pts exhibited a detectable plasma mutation prior to and during treatment with nivolumab (p53 (100%), CDKN2A (28.6%), HRAS (21%) and PI3KCA (7%)). The pt with no mutation detected was HPV+. During treatment, new plasma HRAS mutations emerged in 3 (21%) pts, while nivolumab did not modulate the overall mutation profile. There was trend for better PFS in pts of cohort 1 whose tumors contained none of analyzed mutations (p=0.08) while disruptive p53 mutation status based on Poeta classification was not prognostic. ConclusionsPlasma mutation detection with SafeSEQ is useful in HNSCC for molecular profiling and real-time disease monitoring and may inform clinical trial design. Legal entity responsible for the studyUniversity funding & Company. FundingSysmex-inostics. DisclosureD. Edelstein: Full / Part-time employment: Sysmex-Inostics. K. Stieler: Full / Part-time employment: Sysmex-Inostics. D. Heim: Full / Part-time employment: Sysmex-inostics. F. Holtrup: Full / Part-time employment: Sysmex-inostics. A. Psyrri: Research grant / Funding (institution): Kura; Research grant / Funding (institution): BMS; Advisory / Consultancy: BMS; Honoraria (self): BMS; Honoraria (self): MSD; Advisory / Consultancy: MSD; Honoraria (self): Roche; Advisory / Consultancy: AstraZeneca; Honoraria (self): Leo. All other authors have declared no conflicts of interest.

Selection of systemic therapy in patients with locally advanced and recurrent/metastatic head and neck cancer: RAND-based expert opinion by an Italian multidisciplinary panel.

Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous disease often presenting at an already advanced stage. Cisplatin chemoradiotherapy is the standard treatment for locally advanced disease, although its efficacy varies according to different studies. Thus, treatment selection is a challenge, especially in older patients, who frequently have several comorbidities. Moreover, the majority of patients with recurrent and/or metastatic disease are unsuitable for local treatment, either surgery or radiation therapy. The only treatment option for them is systemic therapy, but prognosis remains poor, with a median overall survival of less than 12 months. A group of Italian key opinion leaders in the field of HNSCC gathered several times in 2018 in order to retrieve a set of statements to help clinicians in their daily decision-making process for the treatment of patients with different scenarios of HNSCC. The panel agreed on 22 statements that were identified as "good clinical points" based on the available literature or after discussion of the most relevant aspect of the underlying diseases when no international consensus was available. The panel identified a number of possible scenarios (namely 71) in which these statements may be helpful to guide decision-making for the best treatment selection.

Value of adjuvant chemotherapy using paclitaxel plus carboplatin after radical surgery with or without radiotherapy in stage IB-iia cervical adenocarcinoma with risk factors.

e17016 Background: The aim of this study was to evaluate the efficacy and safety of paclitaxel/carboplatin as an adjuvant systemic chemotherapy for stage IB-IIA cervical adenocarcinoma patients after radical hysterectomy and pelvic lymphadenectomy with or without radiotherapy(RT). Methods: The cases of all patients (n = 152) with FIGO IB-IIA cervical adenocarcinoma who were treated by radical hysterectomy and pelvic lymphadenectomy with or without RT at Chinese academy of medical sciences cancer institute and hospital between January 2008 and January 2017 were reviewed. Of these, 35 patients displayed high-risk prognostic factors (high-risk group), 65 displayed intermediate-risk prognostic factors meeting sedlis criteria(intermediate-risk group),and 54 cases presented poorly differentiated status or LVSI, without other risk factors. In the high-risk group,18 patients received adjuvant radiotherapy and concurrent cisplatin chemoradiotherapy(RT-CCRT ) and 17 received adjuvant radiotherapy plus systemic chemotherapy using Paclitaxel Plus Carboplatin (RT-CT ). In the intermediate-risk group, 47 patients were treated with RT-CCRT and 16 were treated with RT-CT ,among the patients with poorly differentiated status or LVSI ,20 were treated with adjuvant chemotherapy using Paclitaxel Plus Carboplatin (CT ) and 34 received no further treatment (NFT). Results: In the high-risk group, adjuvant RT-CT was significantly superior to RT-CCRT with regard to median PFS and 2-year PFS rate(93.07months vs 52,44months, 94.1% vs 72.2%), but the recurrence rate and survival rate showed no significantly difference(11.8% vs 33.3%,100% vs 83.3%) . In the intermediate-risk group, Patients receiving RT-CT showed a better 2-year PFS rate and recurrence rate compared to those with RT-CCRT (100% vs 90.7%, 6.3% vs 12.6%), but the differences were not statistically significant. Among the patients with poorly differentiated status or LVSI, addition of adjuvant systemic chemotherapy resulted in significantly improved 2-year PFS rate compared with the NFT group (95% vs. 75.2%,p = 0.032). Conclusions: Adjuvant systemic chemotherapy using Paclitaxel Plus Carboplatin improved the prognosis of FIGO stage IB-IIA cervical adenocarcinoma patients in the high-risk group and patients who presented 2 or more intermediate-risk factors. Early cervical adenocarcinoma patients with low differentiation or LVSI can also benefit from postoperative adjuvant TC chemotherapy.

Impact of Neoadjuvant Chemotherapy on the Administration of Concurrent Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma

ObjectivesThe standard of care for locally advanced nasopharyngeal carcinoma (NPC) is concurrent cisplatin chemoradiotherapy. Neoadjuvant chemotherapy can be administered to downsize tumors before concurrent treatment to optimize radiation volumes. Our hypothesis was that the use of cisplatin in the neoadjuvant phase could limit the amount of cisplatin that patients could tolerate in the concurrent phase of treatment.MethodsThis is a retrospective analysis of Canadian NPC patients who received neoadjuvant chemotherapy with the intention to downsize locally advanced tumors prior to concurrent cisplatin plus radiation. Baseline demographic and treatment data were obtained from institutional databases and chart review; all data were analyzed with SPSS (SPSS Inc. Released 2005. SPSS for Windows, Version 14.0. Chicago: SPSS Inc.) Overall survival (OS), disease-specific survival (DSS), and local/regional relapse-free survival (LRRFS) were analyzed using Kaplan-Meier survival functions. Univariate and multivariate models were used to determine factors associated with the total dose of concurrent chemotherapy.ResultsForty-six patients were identified as receiving neoadjuvant chemotherapy before concurrent chemoradiotherapy. In the univariate and multivariate analyses of patients who received concurrent chemotherapy, receiving over 200 mg/m2 concurrent cisplatin with radiation was associated with a higher neoadjuvant dose of chemotherapy received. The median follow-up time was 2.6 years (range, 0.17 years to 10.6 years). At three years, the OS was 83%, DSS was 86%, and LRRFS was 74%.ConclusionsNPC patients have been treated with neoadjuvant chemotherapy at this center with favorable outcomes. Most patients could tolerate concurrent chemotherapy after radiotherapy. Receiving higher doses of concurrent chemotherapy was associated with also having higher doses of neoadjuvant cisplatin. This suggests that neoadjuvant cisplatin is not a limiting factor in the delivery of full-dose concurrent chemotherapy.

Chemoradiotherapy completion and neutropenia risk in HIV patients with cervical cancer.

Cervical cancer (CC) is one of the acquired immunodeficiency syndrome (AIDS) defining diseases and the human immunodeficiency virus (HIV) infection is thought to relate with increased acute toxicity of chemoradiotherapy (CRT).We investigated the effect of HIV status in the incidence of neutropenia associated with cisplatin-based CRT for CC and its impact in treatment completion.This is a single-center retrospective cohort study. Data collection was performed for all the consecutive stage Ib-IV CC women treated with cisplatin-based CRT from 2012 to 2016, and with known HIV status.Sixty-one patients were included, 6 were HIV+. HIV+ patients had a higher risk of neutropenia at any cycle during cisplatin CRT [adjusted odds ratio (OR) 7.3, 95% confidence interval (95% CI) 1.02–52.3; P = .05]. Despite the absolute differences, mean neutrophil count was nonsignificantly lower in HIV+ women, both at baseline [4455/μL (interquartile range, IQR: 1830–6689) vs 6340 (IQR: 1720–18,970) for HIV−, P = .98] and at the end of treatment [1752/μL (IQR: 1100–2930) vs 3147/μL (IQR: 920–18,390) in HIV−; P = .06]. Moreover, when considering the effect of time, CRT seems to induce a consistent drop of neutrophils in both groups (P = .229). No febrile neutropenia events occurred.In HIV+ women, there were more CT cycle delays (P = .013), patients were more prone to use granulocyte colony-stimulating factor (G-CSF; HIV+ 40.0% vs HIV− 4.0%; P = .04) and less likely to complete at least 5 cycles of cisplatin (P = .02). All patients received adequate dose of pelvic RT, regardless of HIV status.HIV+ patients have a significantly increased risk of neutropenia during CRT treatment for CC and are less likely to complete chemotherapy with cisplatin.

Once-a-week versus once-every-3-weeks cisplatin in patients receiving chemoradiation for locally advanced head-and-neck cancer: A survey of practice in India

Purpose: High-dose (100 mg/m2) cisplatin with radiotherapy is the standard practice in locally advanced head-and-neck squamous cell carcinoma. Use of this regimen in resource- constrained and economically constrained countries like India is difficult. Methods: This study was a cross-sectional survey conducted among Indian oncologists treating head-and-neck cancer. The survey consisted of 25 questions relevant to general day-to-day practice in head-and-neck oncology. It included questions regarding the most common drug used in the concurrent chemoradiation (CRT) setting, the most common schedule of administration of cisplatin, the doses used in once-a-week or once-every-3-week cisplatin chemoradiotherapy, toxicities, and preventive strategies. Descriptive analysis was performed using SPSS software version 20. Results: Responses were obtained from 257 oncologists practicing in various oncology centers throughout the country. The agent most commonly used for radiosensitization was cisplatin (n = 243; 94.6%). The once-a-week regimen of cisplatin was the favored regimen (87.9%, n = 226). The reason for favoring the once-a-week regimen was better tolerance (n = 153, 59.5%). The once-every-3-weeks cisplatin schedule was prescribed for >50% of head-and-neck cancer patients by 23 participants only (8.9%). Conclusion: In this nationwide Indian survey, the majority of clinicians preferred the once-a-week cisplatin schedule for CRT in locally advanced head-and-neck cancer patients, due to better tolerance.

Three-weekly cisplatin or weekly cisplatin chemoradiotherapy for locally advanced head and neck squamous cell carcinoma—the jury is still out

According to cancer statistics for 2012 (GLOBOCAN), the global incidence of HNC in that year stood at around 680,000, with 390,000 of these cases occurring in Asian countries. Around 240,000 Asian people died from HNC, accounting for 5.5% of cancer deaths (1). Traditionally, patients with head and neck squamous cell carcinoma (HNSCC) have a significant smoking and drinking history, and around 60% present with advanced disease (Stage III and IV), for which prognosis remains poor.