Carcinoma Of Oropharynx Research Articles

Checkpoint inhibitors assessment in oropharynx carcinoma (CIAO).

TPS118 Background: Oropharyngeal squamous cell carcinoma (OPSCC) is classified by HPV status. Patients with HPV negative OPSCC have worse prognosis when compared to HPV positive. The epidemic of HPV associated OPSCC emphasizes the need to improve outcomes and reduce treatment related toxicities in this patient population. Taken together, there is an unmet need for novel treatment approaches to improve survival and/or quality of life in patients with OPSCC. Checkpoint inhibitors, particularly anti-PD-1/PD-L1, have shown encouraging activity in metastatic head and neck SCC. Targeting both PD-1 and CTLA-4 pathways may have additive or synergistic activity. Durvalumab and tremelimumab are immune checkpoint inhibitors that target, respectively, PD-L1 and CTLA-4. The optimal integration of novel therapeutics into clinical practice requires a thorough understanding of the molecular effects of treatment that is best evaluated by longitudinal tumor sampling. Minimally invasive transoral robotic surgery (TORS) provides opportunities to leverage standard-of-care surgery to interrogate the tumor microenvironment after neoadjuvant treatment. Methods: This is a randomized, window of opportunity trial evaluating durvalumab single agent or combined with tremelimumab in OPSCC patients amenable to curative intent surgery. The primary objective is to quantify differences in CD8+ TILs between pre- and post-treatment surgical specimens in patients treated with durvalumab vs. durvalumab plus tremelimumab. Secondary objectives include assessing the safety and toxicity of durvalumab plus or minus tremelimumab in the preoperative setting; objective response rate by RECIST at 8 weeks; percentage of patients undergoing surgery at 8 weeks; percentage of viable tumor cells in the surgical specimen; and patient-reported outcomes. Pre- and post- treatment tumor and blood based immune biomarkers will be evaluated and correlated with HPV status, outcomes, and toxicity. Eligible patients must be ≥ 18 years old, have surgically resectable stage II-IVA newly diagnosed OPSCC or loco-regional recurrence from an OPSCC primary ≥ 6 months after completion of curative intent treatment, and have a performance status ECOG 0-1. Enrollment is ongoing. Clinical trial information: NCT03144778.

Study of cutaneous adverse effects of cancer chemotherapy

Background: Cancer is a leading cause of mortality and morbidity in both developed and developing parts of the world with the disease burden projected to grow exponentially in future. Over the past several decades great advances have been made in the area of cancer chemotherapy. Objectives: To study the various cutaneous adverse events associated with cancer chemotherapy. Methodology: 100 patients diagnosed with cancer attending the departments of a tertiary hospital who underwent chemotherapy and satisfied the inclusion and exclusion criteria were included in this study. It is a hospital based observational study. All patients were counselled about the study and informed written consent was obtained. Patients were examined before start of chemotherapy treatment and after every cycle of chemotherapy. Data collected was analysed using SPSS version 16.0. Results: In this study, 100 patients including 37 females and 63 males were included in this study. Majority (56%) of the patients belonged to the age group of 41-60 years. The common indications for chemotherapy were carcinoma oropharynx (24%), carcinoma breast (18%), tongue and stomach. Among the cutaneous adverse events noted, hair changes were the most common presentation and were reported in 68 patients. Skin changes were seen in 65 cases, nail changes in 30 cases and mucosal changes in 12 patients. Xerosis (26%) and hyperpigmentation (22%) were the most commonly observed adverse event affecting skin. Cisplatin, cyclophosphamide, 5 fluorouracil, carboplatin, paclitaxel and doxorubicin were the most frequently prescribed chemotherapeutic drugs. Conclusion: Our observations necessitate a joint effort between dermatology and oncology for the early recognition and adequate treatment of the cutaneous adverse effects associated with cancer chemotherapy which may help in reducing morbidity and improving compliance.

Split-Course radiotherapy: A nonideal treatment in a nonideal patient

Background: Radical chemoradiation is the standard of care for locally advanced head-and-neck cancer. However, patients with pretreatment poor risk features exhibit a poor tolerance to these rigorous regimens and are then usually prescribed short-course palliative radiotherapy which provides symptomatic relief; however, survival outcomes are poor. However, a proportion of these patients may tolerate higher dose of radiation with planned treatment break which in turn may translate into improved locoregional control. Materials and Methods: Patients with histologically confirmed nonmetastatic locally advanced squamous cell carcinoma of oropharynx with poor risk features, treated with split-course radiotherapy were included in this retrospective study. A dose of 35 Gy in 15# 3 weeks was initially prescribed. After planned treatment break of 2 weeks, an additional dose of 25 Gy in 10# 2 weeks was delivered. A weekly assessment of radiation reactions was performed during the treatment course, and response to the treatment was assessed clinically at 8 weeks after treatment completion and on subsequent follow-up. Survival analysis was done at median follow-up. Results: Of the 117 eligible patients, 14 (11.9%) had Stage III (with poor Karnofsky Performance Score) and 103 (88.1%) had Stage IV disease. Toxicity was observed as Grade I 80/117 (68.4%), Grade II 20/117 (17.1%), and Grade III as 17/117 (14.5%). A complete clinical response was observed in 45.3% patients at first follow-up. Patients had a median follow-up of 20 months (range 0–62 months). Median progression-free survival and overall survival were 12 and 16 months, respectively. Conclusions: This regimen can be delivered effectively and has an acceptable toxicity profile. It can be used as a treatment option in patients with poor risk pretreatment features.

Acute toxicity of concomitant boost radiation therapy by volumetric-modulated arc therapy in head and neck cancers

AbstractIntroductionVolumetric-modulated arc therapy (VMAT) is an advanced form of intensity-modulated radiation therapy that reduces treatment time without compromising plan quality. This study assessed acute toxicities in patients having carcinomas of oropharynx, larynx and hypopharynx treated with concomitant boost radiation therapy by VMAT.Materials and methodsIn this study, 30 patients of stages II–IVA disease were treated with concomitant boost radiation therapy using VMAT and those with stages III and IV also received concurrent chemotherapy with cisplatin 100 mg/m2 weekly thrice for two cycles. The total dose was 68·4 Gy/40 fractions/5.5 weeks (1·8 Gy/fraction/day to the large field for 28 fractions +1·5 Gy/fraction/day to boost field for the last 12 days of treatment). Radiation Therapy Oncology Group acute radiation morbidity scoring criteria was used to grade acute effects.ResultsAll patients completed scheduled treatment with median duration of 44 days. No grade 4 skin and mucosal toxicities were observed; grade 3 skin and mucosal toxicities seen in six (20%) and eight (26·67%) patients, respectively; grade 3 dysphagia and laryngeal toxicity in eight (26·67%) and three (10%) patients, respectively; two patients had grade 4 laryngeal toxicity. No grade 3 or grade 4 haematological toxicities were seen.ConclusionVMAT-based concomitant boost radiation therapy allows for dose escalation with good patient tolerance by limiting acute toxicities.

Superiority in Robustness of Multifield Optimization Over Single-Field Optimization for Pencil-Beam Proton Therapy for Oropharynx Carcinoma: An Enhanced Robustness Analysis

To compare the difference in robustness of single-field optimized (SFO) and robust multifield optimized (rMFO) proton plans for oropharynx carcinoma patients by an improved robustness analysis. We generated rMFO proton plans for 11 patients with oropharynx carcinoma treated with SFO intensity modulated proton therapy with simultaneous integrated boost prescription.Doses from both planning approaches were compared for the initial plans and the worst cases from 20 optimization scenarios of setup errors and range uncertainties. Expected average dose distributions per range uncertainty were obtained by weighting the contributions from the respective scenarios with their expected setup error probability, and the spread of dose parameters for different range uncertainties were quantified. Using boundary dose distributions created from 56 combined setup error and range uncertainty scenarios and considering the vanishing influence of setup errors after 30 fractions, we approximated realistic worst-case values for the total treatment course. Error bar metrics derived from these boundary doses are reported for the clinical target volumes (CTVs) and organs at risk (OARs). The rMFO plans showed improved CTV coverage and homogeneity while simultaneously reducing the average mean dose to the constrictor muscles, larynx, and ipsilateral middle ear by 5.6Gy, 2.0Gy, and 3.9Gy, respectively. We observed slightly larger differences during robustness evaluation, as well as a significantly higher average brainstem maximum and ipsilateral parotid mean dose for SFO plans. For rMFO plans, the range uncertainty-related spread in OAR dose parameters and many error bar metrics were found to be superior. The SFO plans showed a lower global maximum dose for single-scenario worst cases and a slightly lower mean oral cavity dose throughout. An enhanced robustness analysis has been proposed and implemented into clinical systems. The benefit of better CTV coverage and OAR dose sparing in oropharynx carcinoma patients by rMFO compared with SFO proton plans is preserved in a robustness analysis with consideration of setup error and range uncertainty.

Reconstruction of oral and maxillofacial soft tissue defects with anterolateral thigh (myocutaneous) flap assisted by computed tomography angiography

To investigate the efficacy of anterolateral thigh (myocutaneous) flap designed with computed tomography angiography (CTA) to reconstruct oral and maxillofacial soft tissue defects. Between January 2011 and December 2015, 23 cases of oral and maxillofacial tumors were treated. There were 14 males and 9 females with the age range from 45 to 72 years (mean, 56.8 years). There were 12 cases of tongue carcinoma, 5 cases of buccal mucosa carcinoma, 4 cases of mouth floor carcinoma, and 2 cases of oropharynx carcinoma; all were squamous cell carcinoma. According to standard TNM staging of the Union for International Cancer Control (UICC), 8 cases were rated as T 2N 0M 0, 3 cases as T 2N 1M 0, 1 case as T 2N 2M 0, 4 cases as T 3N 0M 0, 2 cases as T 3N 1M 0, 2 cases as T 3N 2M 0, 2 cases as T 4N 1M 0, and 1 case as T 4N 2M 0. The course of disease was 1-6 months (mean, 2.4 months). CTA was performed before operation to locate the perforator vessel and its surface projection of emerging point and to design anterolateral thigh (myocutaneous) flap by computer. The defects of soft tissue ranged from 6 cm×4 cm to 11 cm×7 cm after resection of tumor. The flap was used to repair defects, including 14 thinned anterolateral thigh flaps, 7 anterolateral thigh myocutaneous flaps, and 2 anterolateral bilobed flaps; and the flap area ranged from 7 cm× 5 cm to 12 cm×8 cm. The donor sites were sutured directly. CTA showed that myocutaneous perforators penetrated at the fascias of the vastus lateralis muscles in 22 cases with a location rate of 95.7% (22/23). Submandibular fistula occurred in 1 case at 5 days after operation and fistula healed after changed dressings. Other wounds at recipient site and donor site healed at primary stage. Anastomose with 2 vein was performed because of poor venous return in 1 case, and the flap survived. The other flaps survived well. All the patients were followed up 6-36 months (mean, 16.4 months). At 3 months after operation, the simplified recovery standard of speech function and swallow function was established according to the University of Washington Quality of Life Scale (UW-QOL). The speech and swallow function recovered satisfactorily in 22 cases, and not very satisfactorily in 1 case of well differentiated squamous cell carcinoma of the right mouth floor (T 4N 1M 0). No obvious tissue atrophy was observed in 23 cases. No dysfunction was found at the donor site. There was no tumor recurrence in 21 patients; 1 patient accepted the second operation due to lymphonodi metastasis of contralateral neck at 6 months after first operation, who died after 23 months; 1 patient died of distant metastasis at 10 months after first operation. The anterolateral thigh (myocutaneous) flap designed with CTA could well recover the morphology and function of the recipient site.

Impact of waiting time for treatment on survival in patients undergoing radiotherapy for head and neck cancer

BackgroundMost of the patients of head and neck cancers are treated with concurrent chemo radiation or radiotherapy alone. Waiting time prior to radiotherapy is a major problem in many radiotherapy centres with reported delays of 70 days or even more especially in developing countries. ObjectiveThis study aims to determine the impact of waiting time for radiotherapy on survival of patients of head and neck cancer. Materials and methodsPatients of squamous cell carcinomas of larynx, oropharynx, hypopharynx and nasopharynx treated with radiotherapy between January 2012 and December 2015 are considered in this study. A total of 287 patients’ case files were analyzed to explore the effect of delay in starting radiotherapy on overall survival. Data was entered and analyzed using R software(R for Windows, version 3.1.1). Survival analysis was performed on different patient parameters to point-out the effect of waiting time for treatment initiation. ResultsIt has been observed that waiting time for radiotherapy should not cross 45 days to get any survival benefit. However patients will get maximum survival advantage if treatment can be started within 20 days from the date of diagnosis. ConclusionThis study revealed waiting time for radiotherapy has significant impact on survival of head and neck cancer patients. The optimum window period of waiting time for radiotherapy to provide maximal survival benefit to head and neck cancer patients is around 20–45 days.

PO-0606: Mandible osteoradionecrosis in oropharynx carcinoma treated with IMRT: Smoking and tumor size matter

PO-0606: Mandible osteoradionecrosis in oropharynx carcinoma treated with IMRT: Smoking and tumor size matter

Phase IIb trial comparing two concurrent cisplatin schedules in locally advanced head and neck cancer.

Background:Concurrent chemoradiation with 3 weekly cisplatin (100 mg/m2) is the standard of care for locally advanced head and neck cancer. However, this regimen has been shown to be associated with lesser compliance and higher toxicities. Hence, there is a need to explore alternative concurrent cisplatin regimens.Objectives:The objective of this study was to compare the efficacy and toxicities of 3 weekly cisplatin (100 mg/m2) with weekly cisplatin (40 mg/m2) concurrently with radiation in patients with locally advanced head and neck cancer.Patients and Methods:This phase IIb trial randomized 56 patients with Stage III and IV squamous cell carcinoma of oropharynx, hypopharynx, and larynx to Arm A or Arm B. Arm A received cisplatin 100 mg/m2 3 weekly and Arm B received cisplatin 40 mg/m2 weekly concurrently with radiation. The primary end point was disease-free survival (DFS) and secondary end points were overall survival (OS) and acute toxicity. DFS and OS were estimated using Kaplan–Meier method, and log-rank test was used to assess the difference in these distributions with respect to treatment.Results:The 2-year DFS in Arm A and Arm B was 64.5% and 52.8%, respectively (P = 0.67). The OS at 2 years was 71% and 61.1% in Arm A and Arm B, respectively (P = 0.61). There were no significant differences in acute hematological, renal, or mucosal toxicities between the two arms.Conclusion:This study showed a nonsignificant improvement in DFS and OS in the 3 weekly cisplatin arm over the weekly arm with comparable toxicities. The trial is registered with Clinical Trial Registry of India (CTRI registration number: CTRI/2013/05/003703, URL-http://ctri.nic.in).

Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx

Functional mouse double minute-2 (MDM2) promoter variants may alter MDM2 expression and thus affect radiotherapy response and prognosis of squamous cell carcinoma of oropharynx (SCCOP). Thus we assessed association of 2 functional MDM2 promoter variants with recurrence risk of SCCOP. The disease-free survival (DFS) of patients with MDM2rs2279744 TT or MDM2rs937283 AA genotypes was significantly reduced compared with that of patients with corresponding GT/GG or AG/GG genotypes. Multivariable analysis showed patients with TT or AA genotypes had a significantly higher risk of SCCOP recurrence than those with corresponding GT/GG or AG/GG genotypes did. Furthermore, patients with combined risk genotypes of the 2 polymorphisms had significantly worse DFS and a higher recurrence risk than patients with fewer combined risk genotypes did (Ptrend < 0.001). Compared with patients with 0 risk genotypes, patients with 1 or 2 risk genotypes had an approximately 3- or 11-fold increased risk of SCCOP recurrence, respectively. Notably, for both individual and combined polymorphisms, the above similar recurrence risks were particularly higher among patients with human papilloma virus (HPV)-positive tumors. Taken together, our findings suggest that MDM2 promoter variants individually, or more likely jointly, play a role in determining the risk of recurrence of SCCOP, particularly HPV-positive SCCOP.

Lugol Chromoscopy in the Follow-up of Head and Neck Carcinoma.

Introduction:Lugol is helpful in identifying early second primary tumors (SPTs) during oroscopy and pharyngoscopy, but this technique has not been assessed during follow-up visits with these patients.Aim:The aim of this study is to describe the use of Lugol (a low-cost method) to diagnose SPTs in the oral cavity and oropharynx.Methods:Patients treated for squamous cell carcinoma of the head and neck were randomly assigned to two groups. Group A was examined with routine oroscopy and pharyngoscopy without Lugol, and Group B was examined with routine oroscopy and pharyngoscopy without stain and with Lugol. A total of 211 patients were included during 4 years.Results:Six oral and oropharynx carcinomas were detected in Group A. Eighteen oral and oropharynx carcinomas were detected in Group B, twelve of which were not seen without chromoscopy but were detected with Lugol.Conclusion:Lugol increases the detection of malignant lesions compared to routine examination alone.

Oral complications in irradiated head and neck cancer patients - 3D conformal radiotherapy planning vs. 3D conformal radiotherapy planning with magnetic resonance fusion

Introduction/Objective. The incidence of radiation-induced side effects in patients with head and neck (H&amp;N) cancer depends on the planning technique and the irradiation dose, as well as primary tumor location within the H&amp;N region. The aim of our research is to establish the incidence of side effects in patients with H&amp;N cancer treated with conformal radiotherapy planning with computed tomography (CT) or computed tomography fusion with magnetic resonance imaging (CT-MRI fusion). Methods. Prospective analysis was performed on 40 patients with oropharynx carcinoma and on 40 patients with larynx carcinoma prospectively followed after radiotherapy. Forty patients with H&amp;N cancer were irradiated by using 3D conformal radiotherapy planning with CT, while other 40 patients were treated using 3D conformal radiotherapy planning with CT-MRI fusion. In all cases standard fractionation was used at 2 Gy per day, five days a week. Results. Of the total of 80 patients treated, 52 patients (52/80; 65%) reported a side effect and the incidence of complications was higher in patients irradiated with 3D technique planning with CT (31/52; 60% for 3D CT vs. 21/52; 40% for 3D CT-MRI; p = 0.02). There were more complications in chemoradiotherapy group of patients than observed when only radiotherapy was used ? 35/52 RT + HT vs. 17/52 RT (67%: 33% and p = 0.004). Conclusion. 3D radiotherapy technique planned solely on the basis of CT is related to high incidence of toxicity, which significantly affects the quality of life of irradiated patients. 3D conformal radiotherapy planned with CT-MRI fusion reduces the incidence of oral complications. Following the example of developed countries, this technique should be considered as a standard method for irradiating patients with H&amp;N cancer. Planning technique with fusion technique using MR imaging is more suitable for delivering higher doses to the tumor with fewer side effects.

HPV 陽性中咽頭癌と HPV 陽性鼻腔癌の同時性重複例

HPV 陽性中咽頭癌と HPV 陽性鼻腔癌の同時性重複例

365PD The role of Cox-2inhibitor in combination with chemoradiotherapy in head and neck carcinoma to reduce mucositis and other side effects

Background Chemotherapy and radiotherapy-induced oral mucositis represents a therapeutic challenge frequently encountered in cancer patients. This side effect causes significant morbidity and may delay or interruption of treatment plan, as well as reduce theraeutic index. Cyclo-oxygenase 2 (Cox2) is an inducible enzyme primarily expressd in inflamed tissue and tumor. Cox-2 inhibitors have shown promise as radio- and chemosensitizer and reduce radio induced toxicities. We conducted a phase III, randomised, double blind, clinical trial to evaluate the toxicity and efficacy of celecoxib, a selective Cox-2 inhibitor, administered concurrently with chemotherapy, and radiation for locally advanced head and neck. Here we report the first report about the role of Cox-2 inhibitor in acute toxicities. Methods Patients with stage III/IV (locally advance) carcinoma of oropharynx, oral cavity, hypopharynx, larynx or nasopharynx who were referred to the department of radiation oncology were eligible. The end points of this study were acute toxicity, response rate and local control. Patients were treated with chemotherapy and concurrent radiation 60-70GY. Celecoxib (100mg qid) was started on the first day of radiotherapy and was given for a total of 8 weeks. Acute toxicities were evaluated every week by WHO scale. Results 122 patients were recruited to this study (each group with 62 patients), 74 male and 48 female with median age of 55.7 years. We used analysis of variance of repeated measures; both groups had acute toxicity but the toxicity in group B was very significantly induced. Mucusitis in group A was significantly (p < 0.000) better than in group B. In group A dermatitis and weight were better than group B. wBC and Cr in both groups were not different. Conclusions It seems that the use of Cox-2 inhibitors may reduce toxicity, especially mucositis resulting from chemoradioation in head and neck cancer. Legal entity responsible for the study Dr Mojahed Funding Tehran University Medical School - Departman Radiation Oncology Disclosure All authors have declared no conflicts of interest.

35P Clinical significance of expression of cripto-1 in patients of squamous cell carcinoma of oropharynx

35P Clinical significance of expression of cripto-1 in patients of squamous cell carcinoma of oropharynx

35P Clinical significance of expression of cripto-1 in patients of squamous cell carcinoma of oropharynx

35P Clinical significance of expression of cripto-1 in patients of squamous cell carcinoma of oropharynx

De-intensification of adjuvant therapy in human papillomavirus-associated oropharyngeal cancer.

Current adjuvant treatment guidelines for oropharyngeal squamous cell carcinoma treated with primary surgery are based on studies that predate the human papillomavirus (HPV) era. HPV-associated oropharynx carcinoma (HPV-OPC) has a much more favorable prognosis compared to HPV-unassociated cancer and is increasingly considered to be a distinct disease entity due to its unique etiology, presentation, and behavior. Currently, there is significant interest in adjuvant treatment de-intensification of HPV-OPC patients in order to reduce treatment-related toxicity while maintaining excellent clinical outcomes. Here, we review the evidence and rationale underlying the ongoing prospective trials of adjuvant treatment de-intensification for HPV-OPC patients.

The national landscape of human papillomavirus-associated oropharynx squamous cell carcinoma.

The head and neck squamous cell carcinoma (HNC) landscape is evolving with human papillomavirus (HPV) being a rising cause of oropharynx carcinoma (OPC). This study seeks to investigate a national database for HPV-associated oropharynx carcinoma (HPV-OPC). Using the National Cancer Data Base, we analyzed 22,693 patients with HPV-OPC and known HPV status. Chi-square tests and logistic regression models were utilized to examine differences between HPV positive and HPV negative OPC. 14,805 (65.2%) patients were HPV positive. Mean age at presentation was 58.4 years with HPV-HNC patients being 2.8 years younger compared to the HPV-negative cohort (58.4 vs. 61.2 years, p < 0.001). 67.6% of white patients were HPV-positive compared to 42.3% of African American patients and 57.1% of Hispanics (p < 0.001). When combining race and socioeconomic status (SES), we found African American patients in high SES groups had HPV-OPC prevalence that was significantly higher than African American patients in low SES groups (56.9% vs. 36.3%, p < 0.001). Geographic distribution of HPV-OPC was also analyzed and found to be most prevalent in Western states and least prevalent in the Southern states (p < 0.001). The distribution of HPV-OPC is variable across the country and among racial and socioeconomic groups. A broad understanding of these differences in HPV-OPC should drive educational programs and improve clinical trials that benefit both prevention and current treatments.

The role of postoperative chemoradiation for oropharynx carcinoma: A critical appraisal revisited.

A recent review in this journal in which the National Comprehensive Cancer Network's recommendations (based in part on results from the Radiation Therapy Oncology Group 9501 and European Organization for Research and Treatment of Cancer 22931 trials) were criticized warrants comment. To address many of the points and misinterpretations raised in that review, additional data are provided that convincingly support the use of concomitant chemotherapy and radiotherapy in patients who have good performance status and high‐risk pathologic features after surgery for mucosal head and neck squamous cell carcinoma.

Outcome Analysis of Squamous Cell Carcinomas of Oropharynx Based on Primary Site That Were Treated With Definitive Intensity Modulated Radiation Therapy Concurrently With Chemotherapy

Outcome Analysis of Squamous Cell Carcinomas of Oropharynx Based on Primary Site That Were Treated With Definitive Intensity Modulated Radiation Therapy Concurrently With Chemotherapy