Chemotherapy In Head Research Articles

Hypofractionated Versus Conventional Radiotherapy with Chemotherapy in Head and Neck Cancer: A Comparative Study

Head and neck cancers are a group of malignancies that arise from common anatomic sites which include the oral cavity, oropharynx, nasopharynx, hypopharynx, larynx, sinonasal cavities and from the salivary glands. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer in the world and has a five-year survival rate of less than 50%. It has high recurrence rates and metastasis. It is a Prospective Observational, and Comparative Study carried out in 30 patients of Loco-regionally advanced carcinoma of head and neck. The diagnosis of loco-regionally advanced cancers of head and neck was made following AJCC staging. The subjects were divided into two groups with 15 in each arm -Accelerated Hypo Fractionated Arm and Conventional Normal Fractionated Arm. All the patients were systematically interviewed, and clinical details of all the subjects were recorded. Among the 30 patients, the highest performance status of (83.3%) ECOG-1 was observed in both the groups when compared to ECOG-2, which is not statistically significant. Hypofractionated radiotherapy can achieve similar tumour response to conventionally fractionated radiotherapy in HNSCC, although with some increase in toxicity. However, to draw some reasonable conclusion, a study with a broader sample and longer follow-up needs to be performed.

Study of metronomic chemotherapy in cancer patients at a tertiary care centre in South India

The past century has witnessed a vast progress in the field of cancer chemotherapy. Angiogenesis is the foundation of cancer existence. Metronomic chemotherapy by definition is the administration of low dose chemotherapy at regular intervals with no long-standing drug free intervals with the aim to achieve continual blood levels of the chemotherapeutic drug, without the severe toxicity profile or the long-standing drug free breaks as seen in maximum tolerated dose (MTD). We conducted a study with the aim to see the role of metronomic chemotherapy in head and cancers at a teritiary care of south India. Materials and Method: We did a retrospective analysis of patients diagnosed with cancer of the head and neck who received metronomic chemotherapy in a tertiary cancer care centre for one year. A total of 46 patients were included in the study. Patients who were at least 18 years old and who had received metronomic chemotherapy for cancer were included in the study. The subjective response was assessed based upon the patients symptoms and clinical examination, and objective response was assessed using radiological modality wherever available. The study was conducted after having been approved by the institution review board. Data and Statistical Analysis: The Chi Square test was performed to identify the statistical significance between metronomic chemotherapy and the variables analyzed and confidence interval was calculated. Results and Observations: In our study we had 46 patients who were diagnosed with head and neck cancer on metronomic chemotherapy and met the criteria and gave informed consent for participation in the study. The mean age of patients was 57.16 years with 33males and 13females. Majority (54%) were in stage 4 .In this study 74% were symptomatically better, 18% got worse, 4% were stable and 4% had no change in their symptomatic profile. Interpretation and Conclusion: In palliative cancer care patients Metronomic chemotherapy is a good option in countr

Preliminary Experience with Induction Chemotherapy In Head and Neck Malignancy from A Tertiary Cancer Centre

Preliminary Experience with Induction Chemotherapy In Head and Neck Malignancy from A Tertiary Cancer Centre

Predictive classifier for intensive treatment of head and neck cancer.

This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer. This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS). Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011). LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.

Inhibitors of Ceramide- and Sphingosine-Metabolizing Enzymes as Sensitizers in Radiotherapy and Chemotherapy for Head and Neck Squamous Cell Carcinoma.

In the treatment of advanced head and neck squamous cell carcinoma (HNSCC), including oral SCC, radiotherapy is a commonly performed therapeutic modality. The combined use of radiotherapy with chemotherapy improves therapeutic effects, but it also increases adverse events. Ceramide, a central molecule in sphingolipid metabolism and signaling pathways, mediates antiproliferative responses, and its level increases in response to radiotherapy and chemotherapy. However, when ceramide is metabolized, prosurvival factors, such as sphingosine-1-phosphate (S1P), ceramide-1-phosphate (C1P), and glucosylceramide, are produced, reducing the antitumor effects of ceramide. The activities of ceramide- and sphingosine-metabolizing enzymes are also associated with radio- and chemo-resistance. Ceramide analogs and low molecular-weight compounds targeting these enzymes exert anticancer effects. Synthetic ceramides and a therapeutic approach using ultrasound have also been developed. Inhibitors of ceramide- and sphingosine-metabolizing enzymes and synthetic ceramides can function as sensitizers of radiotherapy and chemotherapy for HNSCC.

Matched pair analysis to evaluate the impact of hospitalization during radiation therapy as an early marker of survival in head and neck cancer patients.

Complications from radiotherapy (RT) alone or combined with surgery and/or chemotherapy for head and neck cancer (HNC) sometimes necessitate hospitalization. Our aim was to evaluate the frequency, cause, and survival outcomes associated with hospitalizations in patients undergoing RT for HNC. Using a retrospective single-institution database, we reviewed hospitalization records of HNC patients treated at Roswell Park Comprehensive Cancer Center with definitive or post-operative RT between 2003 and 2017. Patients who were admitted during treatment and within 90-days post-RT were identified. Multivariate analyses, Kaplan-Meier statistics, and analysis on propensity score matching were performed to obtain matched-pair, after matching baseline characteristics, such as age, gender, smoking, tumor staging, p16 status, and treatments received. 839 patients were eligible for analysis. Median follow-up was 34.8months (Interquartile range [IQR] 15.6-64.8). 595 (71%) received definitive RT and 244 (29%) received adjuvant RT. Chemotherapy was used in 671 patients (80%). 171 patients (20%) had at least one hospitalization. Dehydration (40%) and fever (29%) were the most frequent causes of admission. Hospitalized patients had significantly worse overall survival (OS) (Hazards ratio [HR] 1.61, 95% CI 1.26-2.07, p<0.001) and cancer-specific survival (CSS) (HR 1.45, 95% CI 1.07-1.95, p=0.02). 163 matched pairs had median follow-up of 58.6months (IQR 37.6-85.0). Median OS was 34.5months (IQR 13.3-58.0) for hospitalized versus 44.2months (IQR 20.3-78.7) for non-hospitalized patients (p=0.01). This study reveals significantly worse OS and CSS for patients hospitalized during RT for HNC. Hospitalization may be an early marker for worse survival.

Hemomicrocirculation of the oral mucosa as an efficiency indicator of local treatment and preventing complications from radiation and chemotherapy for head and neck malignancies

Hemomicrocirculation of the oral mucosa as an efficiency indicator of local treatment and preventing complications from radiation and chemotherapy for head and neck malignancies

The Slippery Role of Induction Chemotherapy in Head and Neck Cancer: Myth and Reality

Chemoradiotherapy as an alternative to surgery can be offered to patients affected by loco-regionally advanced head and neck cancer (HNC). Induction chemotherapy is a valid option, supported by few positive trials, but its real efficacy is still a matter of debate. The standard regimen for induction chemotherapy in Europe is a combination of docetaxel (75 mg/m2) and reduced dose doses of cisplatin (75 mg/m2) and 5-fluorouracil (750 mg/m2 day, for five consecutive days) (TPF). It is less toxic and more effective than the historical therapy PF (cisplatin 100 mg/m2 and fluorouracil 1,000 mg/m2/day for five consecutive days). However, in some studies treatment-related mortality has been reported to be as high as 6%. Therefore, some less toxic combinations, such as a modified TPF regimen and the combination of carboplatin plus paclitaxel have been studied. These regimens are showing promising results but deserve further validation in comparative trials. Furthermore, several trials are underway in order to enhance TPF with immune checkpoints inhibitors. Compared to chemoradiotherapy, induction chemotherapy followed by chemoradiation was shown to be non-inferior, and it could decrease the distant metastatic progression, especially in high-risk populations. For selected patients, induction chemotherapy could be a strong option. The chemoselective process that leads to immediate surgery for non-responders, the high response rate (complete responses are sometimes observed), and the survival data, are all arguments in favor of induction chemotherapy, if performed in experienced centers involving health professionals in the context of a skilled multidisciplinary team.

Two Cases of Non-occlusive Mesenteric Ischemia after Chemotherapy for Head and Neck Cancer

Two Cases of Non-occlusive Mesenteric Ischemia after Chemotherapy for Head and Neck Cancer

The effect of Hangeshashinto on Oral Mucositis Caused by Induction Chemotherapy in Patients with Head and Neck Cancer.

Oral mucositis (OM) is a side effect of chemotherapy in head and neck cancer. Severe OM often has a large impact on quality of life. Therefore, the treatment of OM during chemotherapy is very important. It was recently reported that Hangeshashinto (TJ-14), a Japanese traditional medicine (Kampo), is effective for OM caused by fluorinated pyrimidine-based agents used in colon cancer. We investigated the efficacy of TJ-14 for OM. We enrolled patients with head and neck cancer who were treated with induction chemotherapy between September 2014 and March 2016. In this double-blind trial, patients were randomly assigned to the TJ-14 group or placebo group. Patients were instructed to dissolve 2.5 g of TJ-14 or placebo in 100 ml of drinking water, rinse their mouths with the solution for 30 s and then spit it out. They were not allowed to eat anything for 30 minutes before or after using the mouthwash. The incidence of ≥ grade 2 OM was 37.5% (three patients) in the TJ-14 group and 50.0% (four patients) in the placebo group, with no significant difference between the two groups. The mean day of onset was 9.7 in the TJ-14 group and 6.7 in the placebo group. The mean duration of ≥ grade 2 OM was 1.3 days in the TJ-14 group and 3.7 days in the placebo group. Thus TJ-14 significantly reduced the duration of ≥ grade 2 OM. Treatment of OM with TJ-14 was associated with a statistically significant reduction in the duration of ≥ grade 2 OM compared to placebo. Gargling with TJ-14 is a safe and effective method of administering the drug to patients with head and neck cancer.

基于计算机文本挖掘的头颈部肿瘤放化疗后口腔粘膜炎基因功能富集及药物治疗分析

基于计算机文本挖掘的头颈部肿瘤放化疗后口腔粘膜炎基因功能富集及药物治疗分析

382P - Drug metabolizing enzymes pharmacogenomic: Biomarkers for improved chemotherapy in head and neck cancer squamous cell carcinoma

BackgroundMuch of the inter-individual differences in the regulation, expression, and activity of drug metabolizing enzymes genes might be crucial factors in defining cancer susceptibility, as well as in determining the efficacy of drugs. Cytochrome P450 (CYP) family of enzymes are the most important drug metabolizing enzymes involved in the metabolism of widely used drugs including anticancer drugs like tamoxifen and cyclophosphamide. Therefore, present study was undertaken to investigate the association of variant genotypes of CYP2C9, CYP2C19 & CYP2D6 with the treatment response (personalized medicine approach) in Head and Neck cancer cases receiving chemotherapy or combination of chemo- and radiotherapy. Methods800 patients suffering from Head & Neck cancer and equal number of age matched controls were included in the study. Genomic DNA was isolated from the blood samples and CYP2C9, CYP2C19 & CYP2D6 genotypes were determined in genomic DNA by PCR based RFLP. Follow-up carried out to correlate the association (if any) in between variants and treatment outcome. ResultsAmongst heterozygous and homozygous variants of CYP2C9*2/*3; CYP2C19*2 /*3 (i.e. CYP2C9*1/*2, CYP2C9*1/*3, CYP2C19*1/*2 & CYP2C19*1/*3) and CYP2D6*4/*10, a high percentage of cases was encountered as non-responders and had toxicities like nausea, vomiting, dizziness etc., as compared to the responders in the same category. In the follow-up study, it was found that a significantly higher number of non-responders (p-value<0.05) were encountered in the cases carrying variant genotypes of either of CYP2C9*2, CYP2C9*3, CYP2C9*2/*3, CYP2C19*2, CYP2C19*3, CYP2C19*2/*3, CYP2D6*4 and CYP2D6*10. ConclusionsIt was demonstrated that CYP2C9, CYP2C19 and CYP2D6 variants modify the treatment outcome in cases receiving combination of radio-chemotherapy. Legal entity responsible for the studyGovernment of India. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

BET bromodomain inhibitor JQ1 promotes immunogenic cell death in tongue squamous cell carcinoma

Drug resistance substantially limits the curative capability of chemotherapy in head and neck cancers such as oral squamous cell carcinoma. Immunosuppression is considered a potential cause of drug resistance. A key discovery in the past decade is that chemotherapeutics can alter tumor cell immunogenicity via inducing release of damage-associated molecular patterns (DAMPs), including ecto-calreticulin (ecto-CALR), high mobility group box 1 (HMGB1) and ATP, causing tumor cells to die in a manner known as bona fide immunogenic apoptosis or immunogenic cell death (ICD). Intriguingly, JQ1 was found in this study to exhibit therapeutic potential in tongue squamous cell carcinoma (TSCC) by inducing ICD. JQ1 induced significant release of calreticulin (CALR), HMGB1 and ATP from Cal27 and SCC7 cells in vitro. Immature dendritic cells (Im-DCs) cocultured with JQ1-pretreated Cal27 cells exhibited significant upregulation of mature markers on their surface and an increase in the secretion of cytokines. In vivo experiments demonstrated that JQ1-pretreated dying SCC7 cells protected immunocompetent mice from rechallenge of SCC7 cells. Intravenous injection of JQ1 efficiently reduced tumor growth and increased tumor-infiltration of CD3+/CD8+ T cells in C3H mice.

The effectiveness of rebamipide mouthwash therapy for radiotherapy and chemoradiotherapy-induced oral mucositis in patients with head and neck cancer: a systematic review and meta-analysis

BackgroundOral mucositis is a frequent and severe adverse event in patients undergoing chemoradiotherapy for head and neck cancers, especially grade 3 or 4 mucositis. Occurrence may result in drop-out from treatment, thereby reducing survival. We aimed to clarify the effectiveness and safety of rebamipide mouthwash for oral mucositis in patients with head and neck cancer receiving treatment.MethodsWe carried out a systematic review and meta-analysis of patients with head and neck cancer who were treated with rebamipide mouthwash. We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL), and the World Health Organization (WHO) International Clinical Trial Registry Platform. The primary outcome was the incidence of severe oral mucositis, and secondary outcomes were time from treatment start to onset of oral mucositis, the response rate of radiotherapy, and any adverse events.ResultsWe included three studies comparing rebamipide versus placebo, all of which evaluating chemoradiotherapy induced oral mucositis. The chemotherapeutic agent was docetaxel in one study and cisplatin in the remaining two. Radiotherapy in each study consisted of 3D-conformal radiation therapy, intensity modulated radiation therapy and conventional radiation therapy, respectively. The calculated odds ratio was 0.29 [95% confidence interval (CI): 0.15 to 0.55], showing a positive association in the three studies between the incidence of grade 3–4 oral mucositis and chemotherapy for head and neck cancer. One study reported an onset of oral mucositis and the time to onset was 14.6 ± 6.4 days for the rebamipide group and 11.2 ± 4.4 days for placebo. One study reported a complete response of 8.3% for placebo and 16.7% for the rebamipide the group, and the partial response was 91.7 and 75.0%, respectively. Adverse events were reported in two studies to be 6.1 and 11.6% for placebo, and 19.4 and 26.0% in the rebamipide group, respectively.ConclusionsRebamipide mouthwash is effective in the prevention of severe mucositis and stomatitis. However, evaluation of adverse events in observational studies are needed.

Role of chemotherapy in 5000 patients with head and neck cancer treated by curative surgery: A subgroup analysis of the meta-analysis of chemotherapy in head and neck cancer

ObjectiveTo evaluate the effect of chemotherapy added to a surgical locoregional treatment (LRT) for patients with locally advanced head and neck squamous cell carcinoma (HNSCC). Materials and MethodsWe studied the sub-group of trials with surgical LRT included in the meta-analysis on chemotherapy in head and neck cancer (MACH-NC). Data from published and unpublished randomized trials comparing the addition of chemotherapy to LRT in HNSCC patients were sought using electronic database searching for the period 1965–2000, hand searching and by contacting experts in the field. Trials with less than 60 patients, or preoperative radiotherapy or where the type of LRT could not be individually determined were excluded. All individual patient data were checked for internal consistency, compared with published reports, and validated with trialists. Data were pooled using a fixed-effect model. Heterogeneity was assessed using Cochrane test and I2 statistic. ResultsTwenty-four trials were eligible (5000 patients). Chemotherapy improved overall survival (HR = 0.92 [95%CI: 0.85–0.99] p = 0.02). There was a significant interaction between treatment effect and timing of chemotherapy (p = 0.08 at pre-specified threshold of 0.10) with a greater effect for concomitant chemotherapy (HR = 0.79, 95%CI: 0.69–0.92). The benefit of chemotherapy was greater in women (HRwomen = 0.63, 95%CI: 0.50–0.80) compared to men (HRmen = 0.96, 95%CI: 0.89–1.04; p for interaction = 0.001). ConclusionsThis analysis confirmed the benefit of concomitant chemotherapy added to surgical LRT. The role of induction therapy as yet to be determined as it did not improve OS. Women may benefit more than men from chemotherapy.

Usefulness of Hematological Inflammatory Markers in Predicting Severe Side-effects from Induction Chemotherapy in Head and Neck Cancer Patients.

Induction chemotherapy (IC) for head and neck cancer (HNC) often causes severe side-effects. However, it has still been challenging to predict the adverse events. The present study aimed to evaluate the role of hematological inflammatory markers in predicting severe side-effects caused by IC. A total of 54 HNC patients who underwent IC were enrolled. The association between severe side-effects and pre-treatment hematological inflammatory markers [the C-reactive protein (CRP) to albumin ratio (CAR), the modified Glasgow Prognostic Score (mGPS), the neutrophil-to-lymphocyte ratio (NLR), and the platelet-to-lymphocyte ratio (PLR)] were evaluated. In the univariate analysis, the incidence of whole severe side-effects (grade 4), febrile neutropenia (above grade 3), and hyponatremia (above grade 3) were significantly higher in the high CAR and high GPS groups. Multivariate analysis revealed that high CAR and mGPS were independent predictors of these side-effects. CAR and mGPS were significant predictors of severe side-effects. These data can potentially offer patients an improved quality of life during cancer therapy.

Revisión sobre prevención y tratamiento de la mucositis oral en cáncer de cabeza y cuello

Introduction: One of the most serious side effects of radiotherapy and chemotherapy in head and neck cancer is oral mucositis or inflammation of the mucosa of the gastrointestinal tract, causing pain and impossibility of a correct intake. Objective: To investigate the interventions that can be developed by the nursing professional to prevent and treat oral mucositis in patients treated for head and neck cancer. Method: A literature search was carried out in PubMed, CUIDEN, CINAHL, Trip, Cochrane, Medes and Epistemonikos databases. Finally, eight articles were selected in which their qualitative analysis was carried out. Results: The most relevant interventions are good oral hygiene and care, saline rinses, sodium bicarbonate, thyme honey and morphine or doxepin solutions, as well as cryotherapy, phototherapy, gabapentin as an adjuvant and Episil® rinse . The use of chlorhexidine is discouraged. Conclusions: Hygiene and oral care are important for the prevention and treatment of mucositis, helping to carry out radiotherapy or chemotherapy without interruptions. The use of mouthwashes, gabapentin, phototherapy and cryotherapy reduce pain and reduce the severity of mucositis.

Intensity modulated radiation therapy and oral mucosa sparing in Head and neck cancer patients: A systematic review on behalf of Italian Association of Radiation Oncology - Head and neck working group.

Oral mucositis is a common dose-limiting toxicity during radiotherapy with or without chemotherapy in head and neck cancer patients. This potentially severe complication globally worsens quality of life and negatively impacts local control and survival's outcomes. Several studies have been published on feasibility and/or clinical benefit of intensity modulated radiotherapy (IMRT) mucosa-sparing technique. In 2017, the Italian Association of Radiation Oncology Head and Neck Cancer Working Group organized a study group to perform a systematic review. The aim was to verify if practical indications, including dose-constraints and demonstrated clinical benefit, could be proposed for oral mucosa (OM)-sparing IMRT in order to reduce the incidence of severe acute mucositis. Although dose to OM should be reduced as much as possible without compromising target volumes coverage, it is still tricky to firmly state that OM-sparing procedure should be considered the standard of care, especially due to high subjective variability in OM contour.

Highlights of This Issue

TP53 is the most commonly mutated gene in solid tumors, and loss of p53 function is strongly correlated with resistance to chemotherapy in head and neck cancer. In this study, Diab and colleagues demonstrate that inhibition of WEE1, a kinase involved in regulating cell cycle transition during S phase and mitosis, has increased efficacy in p53-deficient cells due to incomplete resolution of DNA damage and stalled replication forks. These lesions are carried over across more than one round of cell division, thereby magnifying the effects of genotoxic therapy.Prostate cancer represents an increasing clinical burden, and metastatic prostate cancer has thus far proven incurable. Metastatic prostate cancer primarily localizes to the bones, inducing osteopathy and bone-related adverse events in patients. Here, Zoni and colleagues demonstrate greatly reduced incidences of bone metastatic lesions by blocking MCAM. Ablation of MCAM or blockade with an MCAM-specific monoclonal antibody reduced interactions between prostate cancer cells and osteoblasts in vitro, and significantly reduced the formation of osteolytic lesions as well as overall tumor growth in vivo. Taken together, these data support the potential utility of targeting MCAM to slow or prevent prostate cancer bone metastasis.Cancer cell motility is a key factor in disease progression, and expression of plasminogen activator inhibitor 1 (PAI1) is associated with increased cellular migration and poor prognosis. Here, Humphries and colleagues demonstrate that increased PAI1 expression reprograms cellular energetics, increasing reliance on glycolysis and inducing mitochondrial fission, cytoskeletal rearrangement, and invasiveness both in vitro and in vivo. Targeting this pathway may present a novel means of blocking cell migration and tumor progression.For decades, prostate cancer diagnosis and prognosis have been largely based on Gleason scoring, a histologic grading scale of the disruption of prostate architecture as the disease increases in severity. While effective, the scale is somewhat subjective and can be difficult to apply to the limited tissue samples obtained from biopsy. Here, Randall and colleagues detail a mass spectrometry imaging workflow based on lipid and metabolite abundance that tightly correlate with increasing Gleason score. The data suggest that lipidomics and metabolomics could represent a higher-fidelity, faster means of scoring prostate cancer aggressiveness to support diagnostic efforts in the clinic.

SCT200 Plus Platinum-based Chemotherapy in Head and Neck Squamous Cell Carcinoma

SCT200 Plus Platinum-based Chemotherapy in Head and Neck Squamous Cell Carcinoma