Chemotherapy For Squamous Cell Carcinoma Research Articles

Long-term outcomes of definitive radiation with volumetric modulated arc therapy and concurrent chemotherapy for squamous cell carcinoma of the anus in a regional Australian cancer centre.

Concurrent chemoradiotherapy is the standard of care in the curative intent treatment of squamous cell carcinoma (SCC) of the anus. Volumetric arc therapy (VMAT) is a highly conformal radiation therapy technique that has been implemented to reduce toxicity for these patients. However, there are few reports evaluating the long-term outcomes of VMAT. Thus, we evaluated the survival and toxicity outcomes of anal cancer patients treated in our regional cancer centre undergoing curative intent chemoradiotherapy using VMAT and following the Australian EviQ guidelines. All consecutive patients treated with the VMAT technique for curative-intent definitive chemoradiotherapy for anal SCC at our institution from 2013 until 2022 were retrospectively reviewed for survival and toxicity outcomes. Kaplan-Meier estimates of locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were obtained. In total, 44 patients were analysed. The median follow-up was 48.9 months (Range 7.8-107). 97.7% of patients completed the prescribed radiation therapy and 88.6% chemotherapy. Five patients (11.4%) recurred. Four (9.1%) had isolated local failures, and one (2.3%) had an isolated distant failure. There were no regional nodal failures. The Kaplan-Meier estimates for locoregional control, distant metastasis-free survival, disease-free survival, anal cancer-specific survival and overall survival were 90.3%, 97.7%, 88.1%, 97.1% and 87% at 3 years, and 90.3%, 97.7%, 88.1%, 93.0% and 72.3% at 5 years, respectively. Acute grade 3 genitourinary (GU), gastrointestinal (GI) and skin toxicities occurred in 2.2%, 6.8% and 13.6% of patients, respectively. There were no acute grade 4 toxicities. Late grade 2 GU and GI toxicities occurred in 6.8% and 11.3% of patients, respectively. There were no late grade 3 or 4 toxicities or treatment-related deaths. The 5 -year colostomy-free survival rate was 86.4%. Outcomes for anal SCC after definitive chemoradiotherapy using VMAT in our regional cancer centre results in low rates of grade 3/4 toxicity, high rates of organ preservation and excellent survival outcomes.

Pathologic complete response in patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A systematic review and meta-analysis.

Neoadjuvant chemoradiation and chemotherapy are recommended for the treatment of nonmetastatic esophageal cancer. The benefit of neoadjuvant treatment is mostly limited to patients who exhibit pathologic complete response (pCR). Existing estimates of pCR rates among patients receiving neoadjuvant therapy have not been synthesized and lack precision. We conducted an independently funded systematic review and meta-analysis (PROSPERO CRD42023397402) of pCR rates among patients diagnosed with esophageal cancer treated with neoadjuvant chemo(radiation). Studies were identified from Medline, EMBASE, and CENTRAL database searches. Eligible studies included trials published from 1992 to 2022 that focused on nonmetastatic esophageal cancer, including the gastroesophageal junction. Histology-specific pooled pCR prevalence was determined using the Freeman-Tukey transformation and a random effects model. After eligibility assessment, 84 studies with 6451 patients were included. The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6%-14%), ranging from 0% to 32%. The pooled prevalence of pCR after neoadjuvant chemoradiation in squamous cell carcinomas was 32% (95% CI: 26%-39%), ranging from 8% to 66%. For adenocarcinoma, the pooled prevalence of pCR was 6% (95% CI: 1%-12%) after neoadjuvant chemotherapy, and 22% (18%-26%) after neoadjuvant chemoradiation. Under one-third of patients with esophageal cancer who receive neoadjuvant chemo(radiation) experience pCR. Patients diagnosed with squamous cell carcinomas had higher rates of pCR than those with adenocarcinomas. As pCR represents an increasingly utilized endpoint in neoadjuvant trials, these estimates of pooled pCR rates may serve as an important benchmark for future trial design.

Pathologic complete response among patients with esophageal cancer receiving neoadjuvant chemotherapy or chemoradiation: A meta-analysis.

305 Background: Although neoadjuvant therapy improves overall survival in esophageal cancers, the benefit is largely confined to those with the greatest pathologic response. Current estimates of pathologic complete response (pCR) rates come from individual studies and lack precision. With this study, we sought to estimate summary pCR rates in patients with non-metastatic esophageal cancer who received either neoadjuvant chemotherapy or chemoradiation by conducting a systematic review and meta-analysis of clinical trials. Methods: Studies were identified from the Medline, EMBASE, and CENTRAL database searches. Eligible studies were published in English from 1992-2022 and consisted of clinical trials that focused on incident non-metastatic esophageal cancer or cancer of the gastroesophageal junction. Trials were required to contain at least one arm of patients receiving neoadjuvant chemotherapy (including perioperative) or neoadjuvant chemoradiation (including treatment with induction chemotherapy). Eligible studies had to report pCR in at least 20 patients who underwent neoadjuvant therapy and surgery. Pooled pCR prevalence was determined using the Freeman-Tukey double arcsine transformation and a random effects model. Results: Among 6,575 records first identified, we included 75 studies with 5,988 patients in the meta-analysis. Of the included studies, 38 (51%) were single arm trials, 35 (47%) were randomized trials, and 2 (3%) were non-randomized trials of multiple treatments. Geographically, 28 (37%), 24 (32%), 21 (28%), and 2 (3%) of the included trials were performed in Asia, Europe, North America, and Australia, respectively. Across 91 trial arms that delivered either neoadjuvant chemotherapy or chemoradiation, platinum and fluorouracil-based regimens were the most common (48.4%), followed by platinum and taxane-based regimens (26.4%), regimens that contained platinum-based agents, fluorouracil, and a taxane (13.2%), and other regimens (12.1%). The pooled prevalence of pCR after neoadjuvant chemotherapy in squamous cell carcinomas was 9% (95% CI: 6% – 14%) across 16 studies, ranging from 0%-32%. The pooled prevalence of pCR after neoadjuvant chemoradiation in squamous cell carcinomas was 32% (95% CI: 26% – 39%) across 21 studies, ranging from 8% to 66%. For adenocarcinomas, the pooled prevalence of pCR was 2% (95% CI: 0% – 7%) after neoadjuvant chemotherapy, across 3 studies, and 22% (17% - 27%) after neoadjuvant chemoradiation across 11 studies. Conclusions: In this meta-analysis, we found that under one-third of patients with non-metastatic esophageal cancer who receive neoadjuvant chemo(radiation) experience pCR. As pCR represents an increasingly utilized as an endpoint in neoadjuvant trials, these estimates of pooled pCR rates may serve as an important benchmark for future trial design.

Abstract 5470: Identification of gene amplification based signature as predictors for chemotherapy in squamous cell carcinoma of the lung

Abstract Background: Lung squamous cell carcinoma (LUSC) is the second most popular histologic subtype accounting for 25%~30% of lung cancer. Due to the lack of targeted therapies for LUSC, the prognosis is poor and chemotherapy still plays a full role in the treatment of LUSC patients currently. However, a significant proportion of patients showed a bad response to chemotherapy. The development of predictive biomarkers is urgent. We aimed to identify new chemotherapy biomarkers based on genomic alterations. Methods: We retrospectively analyzed DNA sequencing data of 317 LUSC patients (pts) at West China hospital. We collected the clinical features and progression-free survival (PFS) of 35 pts with chemotherapy only. Pts were assigned to different subgroups based on genomic alterations using non-negative matrix factorization (NMF) clustering. Based on the characteristics of the cluster, we then explored clear gene signatures to predict the prognosis of chemotherapy. The clinical information and sequencing data of TCGA LUSC with chemotherapy were used to validate the prognostic value of the signature. Results: The 317 LUSC pts were grouped into 4 clusters characterized by different genomic alterations. Cluster 1 (C1) had 129 pts and was characterized by TP53 alterations. There were 116 pts in cluster 2 (C2) characterized by PIK3CA amplification (amp). Cluster 3 (C3) had 33 pts and was characterized by gene amp of CCND1, FGF3, FGF4, and FGF19. Cluster 4 (C4) was characterized by gene amp of FGFR1, KDR, KIT, and PDGFRA. The 35 pts treated with chemotherapy only were also classified into 4 clusters. C1 was associated with the shortest PFS (hazard ratio (HR), 2.87; 95% confidence interval (CI), 1.15-7.13; p = 0.018) independently of the clinical stage, but C2, C3, and C4 showed no significant difference. In addition, we also found that pts with TP53 loss of function (LOF) alteration had significantly shorter PFS than those without TP53 LOF (wildtype or not LOF, p = 0.029). So we further modified the clustering by TP53 alteration from C1 and gene amp from C2, C3, and C4. Therefore, 35 pts were then grouped into 3 subtypes based on TP53 LOF and gene amp characteristics, and the PFS was significantly different. Pts (n = 8, 23%) with at least one amp of 9 genes (PIK3CA, CCND1, FGF3, FGF4, FGF19, FGFR1, KDR, KIT, and PDGFRA) but no TP53 LOF had the longest PFS (HR, 0.12; 95% CI, 0.02-0.66; p = 0.011). Pts (n = 6) with TP53 LOF but no 9-gene amp had poor survival compared with pts in other subtypes. This gene signature was validated in TCGA pts. The signature of 9-gene amp without TP53 LOF also indicated the best PFS and TP53 LOF without 9-gene amp indicated the worst PFS (p = 0.081). Conclusion: We develop a biomarker signature that consists of 9-gene amp and TP53 LOF to indicate the prognosis of chemotherapy. Our results suggest that 9-gene amp without TP53 LOF in LUSC is a favorable prognostic marker for patients taking chemotherapy. Citation Format: Yuan Tang, Yuli Li, Ting Hou, Lili Jiang, Hongjie Liu, Chunxiao Pan, Weiya Wang, Li Qiu, Yajing Zhang, Guiping Zhang, Ke Zheng. Identification of gene amplification based signature as predictors for chemotherapy in squamous cell carcinoma of the lung. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5470.

Results of complex treatment of patients with locally advanced squamous cell carcinoma of the paranasal sinuses and nasal cavity using induction chemotherapy

Introduction. About 600 new cases of malignant neoplasms of the paranasal sinuses and nasal cavity are detected annually in Russia. To date, there are no randomized trials to determine the optimal treatment algorithm for this group of patients. Data on the use of induction chemotherapy in squamous cell carcinoma of sino-nasal tract are limited to a small series of clinical observations and, often, are retrospective in nature.Aim. Evaluation of the effectiveness of induction chemotherapy in patients with locally advanced squamous cell carcinoma of the paranasal sinuses and nasal cavity.Materials and methods. Since 2012, 22 patients with locally advanced cancer of the paranasal sinuses and nasal cavity have been treated in our center, who underwent 3-component induction chemotherapy according to the TPF protocol. Evaluation of the effectiveness of treatment was carried out according to the criteria of Response evaluation criteria in solid tumors 1.1 (RECIST 1.1). Patients with a decrease in the tumor size by 30 % or more, were followed by radiation therapy in doses of 66–70 Gy. Patients with a residual tumor underwent surgery after the end of chemoradiotherapy.Results. In 21 patients available for analysis, overall response rate after induction chemotherapy was 71 %: complete response was registered in 3 (14 %) patients, partial response in 12 (57 %), stable disease in 4 (19 %). Progression disease after 3 courses of induction chemotherapy was detected in 2 (10 %) patients.Conclusions. Thus, induction chemotherapy in patients with squamous cell carcinoma of sino-nasal tractseems to be a promising direction for investigation, that can significantly improve the long-term results of treatment of this category of patients and help to avoid of disabling surgery in some of them.

Bioderived deep eutectic solvent-based topical chemotherapy for squamous cell carcinoma of the skin

The properties of deep eutectic solvents (DESs) are tunable, providing a route to new functions. Choline and geranic acid (CAGE) class of DESs shows antimicrobial properties, acts as drug delivery systems, and functions as anti-obesity agents. We hypothesize that new properties are attainable by rational variation of the molar ratios of choline and geranic acid. This study assessed the anticancer properties of a series of CAGE DESs, aiming to develop novel topical chemotherapy for squamous cell carcinoma of the skin. Cell viability assay demonstrated that varying the molar ratio of choline and geranic acid provided a strategy to significantly reduce the viability of human squamous carcinoma of the skin cell line (A431) without compromising the viability of human normal skin fibroblast cell line (CRL-2091). This molar ratio did not induce CRL-2091 to release interleukin–1β (IL–1β), a biomarker of acute and chronic inflammation, suggesting that the therapeutic dose of CAGE is unlikely to trigger skin inflammation. The anticancer property of CAGE is attributable to geranic acid, which also reduced the viability of A431 and CRL-2091 cell lines. With regards to mechanism, the therapeutic dose of CAGE did not rupture the cell membrane but induced oxidative stress on the A431 cell line. Concluding, rationally varying choline and geranic acid molar ratios provides a strategy to endow new properties on CAGE as demonstrated by selective activity against squamous cell carcinoma of the skin.

Patterns of care for relapsed oesophageal cancer after initial curative trimodality therapy: Long-term follow-up of the SAKK 75/08 trial

BackgroundRecurrent oesophageal cancer after the initial curative multimodality treatment is a disease condition with a poor prognosis. There is limited evidence on recurrence patterns and on the optimal therapeutic approach. MethodsWe analysed the pattern of disease recurrence and subsequent therapies in patients with recurrent oesophageal cancer based on prospectively collected data within a predefined subproject of the randomised phase 3 trial Swiss Group for Clinical Cancer Research (SAKK) 75/08. ResultsAmong 300 patients included in the SAKK 75/08 trial, tumour recurrence was observed in 103 patients with a median follow-up of 5.8 years. Locoregional recurrence only was found in 26.2% of the patients, 21.4% of patients had both distant and locoregional recurrence and 52.4% of patients had distant recurrence only. Fifty-nine patients (58%) received at least one line of systemic therapy at recurrence, most commonly oxaliplatin-based combination therapies for adenocarcinoma and single-agent chemotherapy for squamous cell carcinoma. Local therapies, most commonly palliative radiotherapy, were used in 49 patients (48%). Six patients underwent a second curative resection or radiochemotherapy. We found no significant overall survival difference for isolated locoregional recurrence versus distant recurrence (15.1 versus 8.7 months, p = 0.167). In a multivariable Cox regression model, time from oesophagectomy to recurrence and the number of recurrence sites as well as the use of systemic therapy or a second curative local therapy significantly correlated with overall survival. ConclusionsRecurrent oesophageal cancer remains a disease with a poor prognosis and requires multidisciplinary management. A second curative approach for localised disease recurrence may be an option for highly selected patients.

Induction Chemotherapy in Squamous Cell Carcinoma of Tongue—Still a Slippery Role?

Abstract Background Tongue cancers are more common in the Indian subcontinent and a leading cause of morbidity and mortality among oral cavity cancers. Induction chemotherapy has been considered an intriguing and smart option for many reasons, but even after years of studies and debates, its role has not been fully established in the management of tongue cancers. Materials and Methods In this study, we evaluated 17 patients with oral tongue carcinomas with locally advanced stage, enrolled into a protocol of three drug (docetaxel, cisplatin, 5-fluorouracil) induction chemotherapy for three cycles. After completion of the three cycles, patients were clinically and radiologically re-evaluated and surgery was done if locally operable. Results At the completion of three cycles, five patients were partial responders, four patients were complete responders, and five patients had progressive disease after three cycles. Those patients with response underwent surgery. There were no significant morbid intraoperative or postoperative complications observed in seven out of nine patients. At the end of treatment completion, five out of nine patients had tumor residue/high-risk features and were planned for adjuvant radiotherapy. Conclusion For locally advanced oral tongue carcinomas, the role of induction chemotherapy before surgery has been fruitful and its impact on function preservation with acceptable oncological clearance is an emerging alternative. Spacing chemotherapy and radiotherapy reduce the incidence of adverse effects of combined treatment.

Effect of Bio Adhesive Barrier-Forming Oral Liquid on Oral Mucositis Severity and Duration in a Clinical Setting With Concurrent Chemo-Radiation for Patients With Head and Neck Cancer

<h3>Purpose/Objective(s)</h3> Oral mucositis is the most common and debilitating complication in patients undergoing radiotherapy and chemotherapy for squamous cell carcinoma of the head and neck (SCCHN). It is one of the major acute morbidities causing pain and dysphagia leading to treatment breaks and hospitalization which has a major impact on prognosis. Despite the significant detrimental sequelae associated, there is no consensus on the optimum oral care regimen even though different strategies have been put forward to prevent severe mucositis. This study was conducted to evaluate the effect of bio adhesive lipid barrier on oral mucosa, which acts as a mechanical barrier for the treatment of oral mucositis in patients with head-and-neck cancer undergoing concurrent chemo-radiation in a clinical setting <h3>Materials/Methods</h3> Twenty-five patients with Head and Neck cancer proven histopathologically, were enrolled for the study. Patients were required to have symptomatic oral mucositis (RTOG Grade 2 or above) at screening and pain scores of at least 6 on an 11-point Likert scale at screening and on each day before radiotherapy. Patients were administered bio adhesive oral spray 3 times per day from week 4 to week 6 during radiation therapy and oral mucositis pain was assessed in terms of severity and duration over the following 8 hours <h3>Results</h3> During screening, 73% of patients had Grade III and 27% had Grade II Oral mucositis. After treatment, Patients experienced a median 50% decrease in pain intensity up to 1 hour. Treatment resulted in significant pain relief within 5 minutes of application that was evident during the entire 8-hour assessment period. The median pain intensity score reached 3 on Likert scale at 5 minutes following oral application and was maintained till 1 hour (i.e., patients experienced an average 4-point decline in pain intensity from baseline to 1 hour after treatment). Regarding rescue medication, only paracetamol was used in a total of 2 patients (8 %) during the course of the treatment period. None of the patients used opioids as rescue medication. Only 3 patients (12%) had the necessity for Nasogastric tube. Mean difference in weight loss during the treatment ranged from 0.7kg to1.6kg. The oral spray was safe and well tolerated by all patients <h3>Conclusion</h3> The bio adhesive barrier-forming oral liquid is efficacious in reducing pain in patients with oral mucositis undergoing chemo-radiation for head-and-neck cancer and demonstrated its potential value in clinical application. Analgesic effect was immediate, clinically significant and persisted for up to 6 hours. It is well tolerated and the trend towards less Nasogastric tube-dependency and a possible reduction in In-patient time is promising.

Comparison of treatment response assessed by 18F-FDG PET/CT with the histopathological response using tumor regression grading on surgically resected specimen following neoadjuvant chemotherapy in squamous cell carcinoma of esophagus.

For the response assessment after chemotherapy, gold standard is always the histopathological response. However, metabolic response can also guide further treatment. Herein, this study aimed to evaluate metabolic response assessment to neoadjuvant chemotherapy in squamous cell carcinoma esophagus using PET response criteria in solid tumors (PERCIST) criteria with taking histopathological response by tumor regression grading as the standard method. Total fifty-seven patients with squamous cell carcinoma esophagus were enrolled between April 2017 to December 2018 for this prospective study. All patients were undergone for baseline PET scan before going for neoadjuvant chemotherapy. Repeat PET scan was done after neoadjuvant chemotherapy. Operable patients were taken for surgery. Final histological response was assessed by Mandard grading. Three metabolic tools [maximum standardized uptake value (SUVmax), tumor regression grading, PERCIST] were compared. The mean SULpeak of the primary lesion was 11.7 ± 5.5 (median, 10.2, range 5.5-31.8). The average percentage change (%Δ) in SUVmax was 42.9 ± 26.3. On histopathology, 5 (13.1%) patients showed complete pathological response, whereas grade II, III, IV and V in 8 (21.1%), 12 (31.6%), 10 (26.3%) and 3 (7.8%) respectively. On comparison of PERCIST with Mandard grading, agreement analysis showed that there was moderate agreement (k, 0.48). %ΔSUV peak change showed a strong correlation with %ΔSUVmax (P = 0.01) and percentage tumor to liver ratio change (P = 0.01). On comparison, these metabolic response tools showed a weak agreement (k, 0.28 with tumor to liver ratio, k, 0.38 with SUVmax). After neoadjuvant chemotherapy, 18F-fluorodeoxyglucose PET/CT can help to assess the response and guide the treatment. However, a larger study is warranted to evaluate their correlation with pathological response.

Efficacy and safety of nanosomal docetaxel lipid suspension-based chemotherapy in squamous cell carcinoma of the head and neck: A multicenter retrospective study.

Squamous cell carcinoma of the head and neck (SCCHN) is the most common cancer in Indian men. Docetaxel alone or in combination with other chemotherapeutic agents is recommended for the management of SCCHN. The present multicenter, retrospective study was conducted to evaluate the efficacy and safety of a novel docetaxel formulation ‘nanosomal docetaxel lipid suspension (NDLS)’-based chemotherapy in SCCHN. The medical records of patients with SCCHN, who were treated with NDLS-based chemotherapy and followed up between August 2014 and September 2018, were reviewed. The efficacy endpoints were overall response rate [ORR; complete response (CR) + partial response (PR)] and disease control rate (DCR; CR + PR + stable disease) for patients receiving NDLS-based induction or palliative chemotherapy. Overall survival (OS) and safety were also evaluated. Efficacy evaluation was available in 30/34 patients (induction, 20/23; palliative, 10/11). NDLS-based induction chemotherapy showed an ORR and DCR of 95% and a median OS of 43.5 months (follow-up duration, 0.6–80.3 months). For NDLS-based palliative chemotherapy, the ORR and DCR were 50% and the median OS time was 4.6 months (follow-up duration, 1.8 to 14.3 months). At least one adverse event was reported in 82.6% patients. No new safety concerns were reported. Overall, NDLS-based chemotherapy was effective and well tolerated in the treatment of SCCHN.

Pembrolizumab alone or with chemotherapy for squamous cell carcinoma of the head and neck: A cost-effectiveness analysis from Chinese perspective.

The KEYNOTE-048 trial indicated pembrolizumab plus chemotherapy is an appropriate first-line treatment for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), while pembrolizumab monotherapy is optimal for PD-L1 positive patient. This study was powered to determine the most cost-effective strategy for patient with different combined positive score (CPS). A Markov model was developed to predict progression-free survival, disease progression, or death in patients with recurrent or metastatic HNSCC based on data from the KEYNOTE-048 trial. Cost was obtained from West China Hospital, while utilities were referred to published studies. By using Monte Carlo simulations, acceptability curves were depicted to address the uncertainty of model inputs. Compared with cetuximab plus chemotherapy, pembrolizumab monotherapy resulted in an incremental cost-effectiveness ratio (ICER) of $14,995 per quality adjusted life year (QALY) in total population and $22,779 per QALY in patients with CPS≥1. Comparing pembrolizumab plus chemotherapy with standard therapy led to an ICER of $43,230 per QALY in total population and $26,157 per QALY in patients with CPS≥1. For patients with CPS≥20, ICERs yield by immunotherapy with or without chemotherapy exceeded the threshold of willingness to pay we set, when compared with standard therapy. Pembrolizumab plus chemotherapy was dominated by pembrolizumab alone in this patient population. For HNSCC patients with different CPS, pembrolizumab alone was the optimal choice for total population and patients with CPS≥1. Among patients with high CPS, immunotherapy with or without chemotherapy was not preferred over the standard therapy.

A prospective study to compare conventional radiotherapy verses accelerated radiotherapy with concurrent chemotherapy in squamous cell carcinoma of oral cavity

A prospective study to compare conventional radiotherapy verses accelerated radiotherapy with concurrent chemotherapy in squamous cell carcinoma of oral cavity

Preoperative chemotherapy compared with postoperative adjuvant chemotherapy for squamous cell carcinoma of the thoracic oesophagus with the detection of circulating tumour cells randomized controlled trial.

The role of preoperative chemotherapy in the treatment of patients with oesophageal squamous cell carcinoma (ESCC) remains controversial. Chemotherapy followed by surgery was compared with surgery±chemotherapy, and the detection of circulating tumour cells (CTCs) was performed on all enrolled patients. We randomly assigned patients with resectable tumours to the preoperative chemotherapy group (Pre group) or surgery group (patients who were either given or not given adjuvant chemotherapy according to their postoperative lymph node status, Post group). Blood samples were collected 1-3 days before treatment (including preoperative chemotherapy and surgery) and 7 days after surgery for CTC detection. From July 2016 to October 2018, 115 patients were enrolled in the study, of whom 57 were assigned to the Pre group and 58 to the Post group. The proportion of patients with stage III ESCC was 63.16% in the Pre group and 48.28% in the Post group. No patients died during chemotherapy. One patient exhibited a complete response to preoperative chemotherapy, and 13 patients exhibited partial responses. The 2-year progression-free survival (PFS) and overall survival (OS) rates were not significantly different between the Pre and Post groups. In the subgroup analysis, patients with CTC (+) prior to treatments receiving preoperative chemotherapy had a better 2-year PFS (71.90% vs. 38.73%, P=0.0379). In the Cox proportional hazards regression analysis, platelet count was proven to correlate significantly with disease progression (P=0.016), and no factors were proven to correlate significantly with mortality after the factors were balanced in the present analysis. Preoperative chemotherapy improved the short-term PFS when CTC detection was positive prior to any treatment for patients with stage II or III ESCC. CTC detection may be used as an index to guide individualized strategic decisions regarding preoperative chemotherapy, but more evidence is needed.

Presurgical induction chemotherapy for squamous cell carcinoma of the tonsil.

The indications for and efficacy of induction chemotherapy in the management of squamous cell carcinoma of the head and neck is controversial. With the advent of human papillomavirus (HPV)-related cancers, survival has improved significantly. Here we present a group of patients with tonsil cancer treated with induction chemotherapy followed by surgery. Retrospective cohort study. Thirty-eight patients with tonsil cancer were treated with induction chemotherapy, consisting of cisplatin and docetaxel, followed by neck dissection and radical tonsillectomy. Twenty-six patients were HPV+, 28 were nonsmokers or long-term former smokers, and 28 were T1/T2. Fourteen patients required postoperative chemoradiotherapy (CRT). Median follow-up time was 4.1 years. A complete response to induction chemotherapy was achieved in 45% (17) of patients. In total, 76% (29/38) of patients were successfully treated: 53% (20/38) with chemotherapy and surgery alone, and 24% (9/38) required postoperative CRT. Almost 90% (23/26) of HPV+ and half (6/12) of HPV- patients are no evidence of disease (NED). HPV status is a significant prognostic factor (P = .02). Only 38% (5/13) of current smokers were NED compared to 96% (24/25) of nonsmokers (P = .0002). All HPV+ nonsmokers (20/20) were NED at last follow-up. In this study, the primary driver of prognosis was smoking status. HPV status and T stage were also important. The prognosis for HPV+ nonsmokers is extremely good; most likely regardless of treatment. Treatment failures have a poor chance of salvage, irrespective of treatment type. With the major exception of HPV- smokers, induction chemotherapy followed by surgery with selective CRT is a viable treatment option for tonsil cancer. 4 Laryngoscope, 130:1206-1211, 2020.

Revised Modelling of the Addition of Synchronous Chemotherapy to Radiotherapy in Squamous Cell Carcinoma of the Head and Neck-A Low α/β?

Background: The effect of synchronous chemotherapy in squamous cell carcinoma of the head and neck (SCCHN) has been modelled as additional Biologically Effective Dose (BED) or as a prolonged tumour cell turnover time during accelerated repopulation. Such models may not accurately predict the local control seen when hypofractionated accelerated radiotherapy is used with synchronous chemotherapy. Methods: For the purposes of this study three isoeffect relationships were assumed: Firstly, from the RTOG 0129 trial, synchronous cisplatin chemotherapy with 70 Gy in 35 fractions over 46 days results in equivalent local control to synchronous cisplatin chemotherapy with 36 Gy in 18# followed by 36 Gy in 24# (2# per day) over a total of 39 days. Secondly, in line with primary local control outcomes from the PET-Neck study, synchronous cisplatin chemotherapy with 70 Gy in 35# over 46 days results in equivalent local control to synchronous cisplatin chemotherapy delivered with 65 Gy in 30# over 39 days. Thirdly, from meta-analysis data, 70 Gy in 35# over 46 days with synchronous cisplatin results in equivalent local control to 84 Gy in 70# over 46 days delivered without synchronous chemotherapy. Using the linear quadratic equation the above isoeffect relationships were expressed algebraically to determine values of α, α/β, and k for SCCHN when treated with synchronous cisplatin using standard parameters for the radiotherapy alone schedule (α = 0.3 Gy−1, α/β = 10 Gy, and k = 0.42 Gy10day−1). Results: The values derived for α/β, α and k were 2 Gy, 0.20 and 0.21 Gy−1, and 0.65 and 0.71 Gy2day−1. Conclusions: Within the limitations of the assumptions made, this model suggests that accelerated repopulation may remain a significant factor when synchronous chemotherapy is delivered with radiotherapy in SCCHN. The finding of a low α/β for SCCHN treated with cisplatin suggests a greater tumour susceptibility to increasing dose per fraction and underlines the importance of the completion of randomized trials examining the role of hypofractionated acceleration in SCCHN.

Retrospective Analysis of Cisplatin Nephrotoxicity in Patients With Head and Neck Cancer Receiving Outpatient Treatment With Concurrent High-dose Cisplatin and Radiotherapy.

Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck (SCCHN), with nephrotoxicity considered the dose-limiting toxicity. The purpose of our study was to propose an outpatient high-dose cisplatin protocol aimed at preventing nephrotoxicity and to analyze the results of its utilization in patients with SCCHN treated with concurrent radiotherapy. We retrospectively evaluated 82 SCCHN patients treated with outpatient high-dose cisplatin concurrent with radiotherapy at our institution. Acute kidney injury (AKI) and chronic kidney disease were defined by Kidney Disease Improving Global Outcomes criteria. Associated factors were identified using analysis of covariance models for categorical variables and adjusted Pearson correlations for continuous variables. The incidence of AKI during treatment was 34.2%. With a median follow-up of 25.7 months, the average decrease in estimated glomerular filtration rate was 12.57 mL/min/1.73 m (SD=18.58). At 1 year and at last follow-up, 5.4% and 4.4% of patients had estimated glomerular filtration rate <60 mL/min/1.73 m. Predictors associated with AKI and chronic kidney disease were: lower baseline weight and creatinine, higher baseline creatinine clearance, smoking, female sex, African American race, hypertension, and increased hydration and magnesium replacement requirements. We encountered limited early and late nephrotoxicity. Importantly, nephrotoxicity was not the main dose-limiting toxicity. Our results emphasize the importance of close monitoring and additional replacement of water and electrolytes as needed. A consistent method of measuring and reporting chemotherapy-induced nephrotoxicity would be a valuable contribution to the literature.

Significance of Perioperative Chemotherapy in Squamous Cell Carcinoma of the Upper and Lower Urinary Tract.

To evaluate the clinicopathological characteristics and prognosis of squamous cell carcinoma (SCC) of the urinary tract (UT) urothelium, and investigate the utility of perioperative chemotherapy. Thirty-three patients diagnosed with SCC in renal pelvis, ureter and bladder at the Kanazawa University between 2007 and 2017 were included in this retrospective study. Cancer-specific survival (CSS) rates according to cancer stage and neoadjuvant chemotherapy (NAC) were determined. Among the entire cohort, two-year CSS rates were 100%, 75%, 47% and 0% in stages I, II, III and IV, respectively, with a significant correlation between CSS and cancer stage (p=0.0063). Sixteen patients underwent radical surgery, and seven patients received NAC; however, there were no significant differences in CSS rates among patients stratified by NAC (p=0.7043). Worse cancer stage for SCC of UT urothelium was associated with worse prognosis. Given the poor efficacy of NAC in these patients, surgical treatment should be preferred.

A comparative analysis between pegfilgrastim and lenograstim administered to patients receiving cytotoxic chemotherapy for squamous cell carcinoma of the esophagus

A comparative analysis between pegfilgrastim and lenograstim administered to patients receiving cytotoxic chemotherapy for squamous cell carcinoma of the esophagus

Low-dose hyperthermia enhances the antitumor effects of chemotherapy in squamous cell carcinoma.

Esophageal squamous cell carcinoma is a highly aggressive neoplasm and the sixth leading cause of global cancer-related death; the 5-year survival rate for esophageal cancer is only about 20%-25% for all stages. Therefore, improving the therapeutic effect is important. This study assessed whether low-dose hyperthermia (LDH) enhances the antitumor effects of chemotherapy. The antitumor effect of chemotherapy with/without LDH in the squamous cell carcinoma cell line SCCVII was evaluated. A comprehensive analysis was performed with real-time polymerase chain reaction (PCR) to study the hyperthermia-induced changes in the gene expression of SCCVII cell lines. In addition, the cytotoxic and apoptotic changes in the cells treated with LDH combined with/without 5-fluorouracil (5-FU) were measured. LDH combined with 5-FU (10 nM) strongly inhibited the cell growth of SCCVII, with flow cytometry showing an increased population of apoptotic cells. PCR showed that LDH promoted a 25.22-fold increase of p53 mRNA and 18.08-fold increase of Bax mRNA in vitro. MDR1 expression was decreased to 28.7% after LDH. This treatment can result in much higher efficacy of antitumor drugs. After LDH, the expressions of TS decreased to 12.06%, OPRT increased by 4.17-fold, and DPD did not change (1.03-fold). This transformations will induce susceptibility to 5-FU. LDH may be a useful enhancer of chemotherapy drugs for squamous cell carcinoma.