Paclitaxel with cisplatin in concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma

The aim of this study was to evaluate the efficacy and the toxicity of paclitaxel and cisplatin in patients in concurrent radiotherapy for locally advanced nasopharyngeal carcinoma, and to see whether such a regime would be better tolerated than high dose cisplatin plus fluoracil in Chinese patients. Thirty-one patients with locally advanced nasopharyngeal carcinoma were enrolled. Patients were scheduled to receive two courses of concomitant chemotherapy, starting on day 1 and then day 28 during radiotherapy (70–76 Gy in 35–38 fractions in 7–7.5 weeks). Chemotherapy was given by intravenous infusion, paclitaxel 120 mg/m² in 3 h, cisplatin 75 mg/m² (25 mg/m² days 1–3). Adjuvant therapy was paclitaxel 135 mg/m² in 3 h, cisplatin 75 mg/m² (25 mg/m² days 1–3) on weeks 3, 6, 9 after radiotherapy. All patients completed radiotherapy, but for concomitant chemoradiotherapy, 20 of the 31 patients completed the 2 cycles of chemotherapy, while the other 11 could only receive 1 cycle due to various reasons. The median follow-up was 40 months, 2 patients developed locoregional recurrences, one of whom in the cervical lymph nodes, the other in the nasopharynx. The 3-year overall survival rate was 83.9% and the distant metastasis rate at 3 years was 13.6%. Grade 3–4 toxicities were neutropenia 12.9%, anaemia 6.45%, thrombocytopenia 3.22%, severe arrhythmia 3.2%, and hypersensitivity reaction 3.2%. In conclusion, paclitaxel with cisplatin as concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma is feasible, safe, and might improve regional control and survival rates in Chinese patients.     

Neoadjuvant docetaxel and cisplatin chemotherapy followed by local irradiation is highly active on locoregionally advanced squamous cell carcinoma of the head and neck

The purpose of this study was to determine the treatment outcome of neoadjuvant docetaxel and cisplatin chemotherapy followed by local radiotherapy for chemotherapy-na?ve patients with locoregionally advanced squamous cell carcinoma of the head and neck. Thirty-seven patients with stage III or IV squamous cell carcinoma of the head and neck who received docetaxel and cisplatin regimen for a maximum of three cycles followed by radiation therapy were enrolled in this study. The overall response rate to the regimen was 91.9 per cent (34 of 37) (the complete remission rate was 48.6 per cent). The median time to treatment failure was 38 months (95 per cent confidence interval, 15-61 months). The four year estimated overall survival rates were 85.1 per cent. The most frequent moderate-to-severe toxicity was grade 3-4 neutropenia. The most common acute non-haematologic toxicities included anorexia, nausea and asthenia. Neoadjuvant docetaxel and cisplatin chemotherapy followed by radiotherapy is a feasible treatment strategy for patients with locoregionally advanced squamous cell carcinoma of the head and neck.     

Neoadjuvant chemotherapy plus intensity-modulated radiotherapy versus neoadjuvant chemotherapy plus concurrent chemoradiotherapy for ascending or descending types of nasopharyngeal carcinoma: A retrospective study

PurposeThis study aimed to compare the efficacy between neoadjuvant chemotherapy (NACT) plus intensity-modulated radiotherapy (IMRT) and NACT plus concurrent chemoradiotherapy (CCRT) in patients with nasopharyngeal carcinoma (NPC).Materials and methodsData from 603 patients with ascending (T4 and N0–1) or descending (T1–2&N3) NPC who were treated at Sun Yat-sen University Cancer Center between October 2009 and February 2012 were retrospectively analyzed. These patients were divided into two groups: NACT+IMRT (n = 302) and NACT+CCRT (n = 301). The primary endpoint was overall survival (OS), which was analyzed using the Kaplan-Meier method, log-rank test, Cox proportional hazards model, and landmark analysis.ResultsIn univariate analysis, there was no significant difference in 5-year OS between the NACT+IMRT and NACT+CCRT groups (hazard ration [HR]: 0.69; 95% confidence interval [CI]: 0.47–1.01; P = 0.057). However, after adjustment for age (<45 years, ≥45 years), gender, histological stage (I/II, III), T stage (1/2, 3, 4), and N stage (0/1, 2/3), NACT+IMRT was more effective in improving OS, with a 33% decrease in the risk of death than NACT+CCRT (HR: 0.67; 95%CI: 0.45–0.99). Furthermore, landmark analysis indicated that patients in the NACT+IMRT group had higher OS rates within 24 months (HR: 1.83; 95%CI: 1.00–3.34), whereas those treated with NACT+CCRT had higher OS rates after 24 months (HR, 0.47; 95% CI, 0.29–0.77). We also found significant survival benefits of NACT+IMRT regimen in patients younger than 45 years old (HR: 0.27; 95%CI: 0.14–0.49), and in those at stage T3 (HR: 0.50; 95%CI: 0.27–0.93) and stage N2/3 (HR: 0.52; 95%CI: 0.32–0.83).ConclusionPatients with ascending or descending NPC who are treated with NACT+IMRT may have better long-term survival outcomes than those treated with NACT+CCRT, especially the patients younger than 45 years old or in stage T3/N2/N3. Additionally, NACT+IMRT may be a better option than NACT+CCRT in patients within the first 24 months.     

Functional organ preservation after chemoradiotherapy in elderly patients with loco-regionally advanced head and neck squamous cell carcinoma

The aim of the present investigation is to evaluate the outcome after induction chemotherapy and concurrent multi-drug chemoradiotherapy (IC/CCRT) with or without post-chemoradiation neck dissection in medically fit elderly patients with loco-regionally advanced head and neck squamous cell carcinoma (HNSCC). Retrospective study including 44 elderly patients (median age 71 years; range 66–77 years) with previously untreated, inoperable, histologically proven non-metastatic stage III or IV HNSCC. Following one cycle of IC, two cycles of cis-platinum and 5-fluorouracil CCRT with conventional fractionated radiotherapy up to a dose of 66–70 Gy were administrated. A neck dissection was recommended for patients with node metastasis larger than 3 cm regardless of the response to therapy and for patients who had suspected persistent neck disease 8–12 weeks after completing treatment. Salvage surgery was considered for histologically proven persistent or recurrent tumor in the primary site. Time-to-event data were described using Kaplan–Meier actuarial curves. Overall, 37 patients (84.1%) completed the planned treatment. There were no cases of treatment-related deaths. Twenty-nine patients (65.9%) developed severe toxicities with grade 4 toxicity accounting for 22.7%. The median follow-up time in survivors was 41 months. Three-year overall survival, progression-free survival, and functional progression-free survival estimates were 70.9, 67.0, and 57.3%, respectively. In selected medically fit elderly patients with loco-regionally advanced HNSCC, cis-platinum-based chemoradiotherapy can be successfully applied, with moderate adverse events, in attempt to preserve a functional upper aerodigestive tract.     

Induction chemotherapy with paclitaxel and cisplatin followed by radiotherapy for larynx organ preservation in advanced laryngeal and hypopharyngeal cancer offers moderate late toxicity outcome (DeLOS-I-trial)

A prospective multicenter phase-II trial (12 centers) was performed by the German larynx organ preservation group (DeLOS) to evaluate the effect of induction chemotherapy (ICHT) with paclitaxel/cisplatin (TP), followed by accelerated-hyperfractionated (concomitant boost) radiotherapy (RT) in responders. The trial was focused on larynx preservation, tumor control, survival, salvage surgery and late toxicity in patients with advanced larynx/hypopharynx carcinoma eligible for total laryngectomy (LE). Seventy-one patients (40 larynx, 87.5% St. III, IV; 31 hypopharynx, 93.4% St. III, IV) were enrolled into the study and treated with ICHT (200 mg/m² paclitaxel, 100 mg/m² cisplatin; day 1, 22) according to the DeLOS protocol. Patients with complete or partial tumor response proceeded to RT (69.9 Gy in 5.5 weeks). Non-responders received a LE followed by postoperative RT (56–70 Gy in 5.5–7 weeks). The response rate to ICHT for larynx cancer was 69.6% (7.1% complete, 62.5% partial response) and for hypopharyngeal cancer was 84.3% (6.9% complete, 77.4% partial response). Overall survival after 36 months was 60.3% (95% CI, 48.4–72.2%), after 42 months was 56.5% (95% CI, 44.2–68.8%). Laryngectomy-free survival was as follows: after 36 months, 43.0% (95% CI, 30.9–55.0%); after 42 months, 41.3% (95% CI, 29.3–53.3%). Both parameters did not show different outcomes after distinguishing larynx from hypopharynx. LE was indicated in 15 non-responders after ICHT. Five of the 15 non-responders refused the laryngectomy. Two of the five received RT instead and had no evidence of disease 42 months after RT. Late toxicity (dysphagia III, IV LENT SOMA score in laryngectomy-free survivors: after 6 months, 1.8%; 12 months, 11.4%; 18 months, 14.5%; 24 months, 8.1%; 36 months, 16%) and salvage surgery (4 pharyngocutaneous fistulas in 27 operations) were tolerable. In a large portion of patients eligible for LE, the larynx could be preserved with satisfying functional outcome. Good responders after ICHT had also a good general outcome with relatively rare severe late toxicities. Due to a slight increase of relevant late dysphagia, functional outcome regarding swallowing and tracheotomy free breathing should be more focused in future larynx organ preservation trials. This trial was initiated and conducted by the German Larynx Organ Preservation Study Group (DeLOS) which was founded as collaboration between head and neck surgeons and radiation oncologists to focus on the role of multimodality treatment in advanced laryngeal and hypopharyngeal cancer in Germany.     

局部晚期鼻咽癌新辅助化疗联合同步放化疗

鼻咽癌是我国南部地区最常见恶性肿瘤之一,大部分患者被发现时已处于局部晚期.鼻咽癌对放、化疗比较敏感,过去认为同步放化疗方案是鼻咽癌的标准治疗方式;研究显示新辅助化疗联合同步放化疗对局部晚期鼻咽癌患者的治疗效果更佳.然而调强放疗与传统放疗技术相比,在保证原有治疗效果基础上可进一步降低患者的毒副反应.本文比较在传统放疗与调强放疗技术两种情况下,同步放化疗与同步放化疗联合新辅助化疗的两种方案对局部晚期鼻咽癌患者治疗效果做一综述.     

Sequential external beam radiotherapy and high-dose-rate intracavitary brachytherapy in T1 and T2 nasopharyngeal carcinoma: an evaluation of long-term outcome

OBJECTIVES/HYPOTHESIS: The standard treatment for nonmetastatic nasopharyngeal carcinoma (NPC) is external beam radiotherapy (EBRT), with or without chemotherapy. Because local control in NPC is an independent prognostic factor for distant metastases and survival, various dose-escalation strategies have been used to reduce recurrences at the primary site. The objective of this report was to evaluate the outcome of adjuvant high-dose-rate intracavitary brachytherapy (HDRIB) in patients with T1 and T2 NPC. STUDY DESIGN AND METHODS: Thirty-three consecutive patients with T1 and T2 NPC were treated prospectively according to a standardized institutional protocol between March 1999 and July 2001. Seventeen patients with stage I/II disease were treated with EBRT to 66 Gy followed by HDRIB (10 Gy in 2 weekly 5 Gy fractions). The remaining 16 patients with Stage III to IVb disease received chemotherapy in addition to radiation. All patients were assessed for treatment response, local control, survival, and toxicity. RESULTS: Median follow-up for all surviving patients was 67 (range 52-76) months. Local failure occurred in two patients; both subsequently underwent successful salvage treatments. Three patients died of metastatic disease, whereas two died of unrelated causes. Five year local control, overall survival, and disease-free survival rates were 93.8%, 83.9% and 78.4%, respectively. All patients experienced acute or late radiotherapy-related sequelae. However, no grade 4/5 toxicities were reported. Specifically, toxicities that could be attributed to brachytherapy were not seen, except for in one patient who developed severe choanal stenosis. CONCLUSIONS: EBRT supplemented by HDRIB produced superior local control rates for T1 and T2 NPC at 5 years of follow-up, with acceptable rates of acute and late toxicities.     

Preliminary results of nasopharyngeal carcinoma treated with intensity-modulated radiotherapy: a retrospective study of 364 patients

The aim of the study was to evaluate the survival and toxicity of 364 patients with nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). Cisplatin-based chemotherapy was given to patients with local–regionally advanced disease. The median follow-up was 26 months (range 3–62 months). The 2-year local failure-free survival, regional failure-free survival (RFFS), distant metastasis-free survival (DMFS) and overall survival (OS) were 97.6, 96.8, 89.1 and 93.5 %, respectively. Overall disease failures (at any site) were found in 60 patients. Eighteen patients experienced locoregional failures: seven were local only, seven were regional only and four were both local and regional. Forty-two patients developed distant metastases. Of these, 30 patients had single organ metastasis and 12 had multiple organ metastases. The most common acute toxicities were dermatitis, mucositis and xerostomia. Grade 0–2 dermatitis, mucositis and xerostomia occurred in 337 patients (92.6 %), 204 patients (56.1 %) and 364 patients (100 %), respectively. Grade 3 dermatitis, mucositis and xerostomia were seen in 27 patients (7.4 %), 160 patients (44 %) and 0 patients. No Grade 4 acute toxicities were observed. N stage was an independent prognostic factor for RFFS, DMFS and OS. Our preliminary results showed that IMRT provides excellent local–regional control for NPC, with acceptable acute toxicities. Distant metastasis remains the most difficult treatment challenge. More effective systemic chemotherapy should be explored.     

T-status and an oral fluoropyrimidine,S-1, adjuvant chemotherapy are prognostic factors in reduced-RADPLAT for resectable hypopharyngeal cancer

Conclusion: Reduced-RADPLAT for HPC achieved comparative survival and locoregional control rates with lower toxicities compared with concurrent chemoradiotherapies including original RADPLAT. S-1 adjuvant chemotherapy showed a survival benefit. Objectives: To evaluate the efficacy and toxicities of targeted intra-arterial (IA) infusion of cisplatin with concurrent radiotherapy with a reduced dose (reduced-RADPLAT) for resectable hypopharyngeal cancer (HPC). Methods: Between 1999–2012, 50 patients with stage II–IVA HPC primarily treated by reduced-RADPLAT were analyzed. They were treated by 2–5 courses of IA cisplatin infusion (100?mg per body) with simultaneous systemic infusion of sodium thiosulfate concurrent with conventional radiotherapy (66–70?Gy). After 2003, S-1, an oral fluoropyrimidine, adjuvant chemotherapy was administered to all eligible patients. Results: During a median follow-up of 48.6 months, the estimated 3- and 5-year overall survival (OS), progression-free survival (PFS), locoregional control, and laryngoesophageal dysfunction-free survival (LEDFS) rates were 76.0% and 62.0%, 58.0% and 50.0%, 66.0% and 62.0%, and 56.0% and 54.0%, respectively. Grade 3 toxicities were observed in 30.0%. No patient had grade 4 or higher toxicities. No patient required tube feeding or tracheotomy at 3 months after treatment. T4-lesions and S-1 administration were significant factors predicting poor and good OS, PFS, and LEDFS, respectively.     

Treatment of neck nodes after induction chemotherapy in patients with primary advanced tumours

Responsiveness of neck nodes to induction chemotherapy often differs from that of the primary tumour. We have conducted a retrospective study to evaluate the results of treating the neck in a cohort of 350 patients with locally advanced (T3–4) head and neck carcinomas treated with radiation therapy at the primary location of the tumour after induction chemotherapy. One hundred and thirty-nine patients (40%) did not have neck nodes on diagnosis (N0). The treatment of the neck included surgery in 65 patients. Neck dissections were carried out before radiotherapy in 37 patients and after radiotherapy in 28 patients. The frequency of neck treatment failure was 24%. There was a tendency to better neck control when treatment included neck dissection, independently of the neck stage or response to chemotherapy. This tendency was statistically significant in patients with an advanced regional tumour (N2–3) who did not achieve a complete regional response after chemotherapy. In a multivariate analysis the variables that were related to the regional failure were the relapse of the tumour at the primary site, the neck stage (N), the type of treatment used in the neck, and the grade of regional response after induction chemotherapy. Our results lead us to suggest that after induction chemotherapy neck surgery is advisable in all cases with advanced regional disease (N2–3), independently of the grade of response achieved after induction chemotherapy, and is also advisable in N1 patients in whom induction chemotherapy does not achieve a complete response. Received: 27 December 1999 / Accepted: 6 June 2000     

Dosimetric parameters associated with conductive or sensorineural hearing loss 5 years after intensity-modulated radiation therapy in nasopharyngeal carcinoma

Background: Most previous studies are separate dosimetric analyses of conductive or sensorineural hearing loss, and they are not conducive to a comprehensive assessment of auditory radiation damage.

Aims/objectives: Our study aimed to evaluate the long-term incidence of sensorineural hearing loss (SNHL) or conductive hearing loss (CHL) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiation therapy (IMRT), and to investigate the relationship between SNHL or CHL and patient factors, treatment-related factors, and radiation dose parameters.

Material and methods: Seventy patients (117 ears) with NPC, who were also treated with IMRT in our hospital from 2006 to 2014, were retrospectively analyzed. Radiation doses to the Eustachian tube (ET), middle ear (ME), cochlear (Co), and internal auditory canal (IAC) were assessed. Pure tone audiometry and impedance audiometry were performed before and during the follow-up period. The relationships between low-frequencies (0.5–2?kHz) or high-frequency (4?kHz) SNHL/CHL and radiotherapy dose parameters were analyzed.

Results: Of the 117 ears studied, 7.69% had low-frequency SNHL, 35.9% had high-frequency SNHL, 23.93% had low-frequency CHL, and 18.80% had high-frequency CHL. The incidence of high-frequency CHL was higher in the T4 group than in the T (1–3) group (p?<?.05). When IAC D_max?>?42.13?Gy or IAC D_mean?>?32.71?Gy, the risk of high-frequency SNHL increased in NPC patients. When ME D_max?>?44.27?Gy, ME D_mean?>?29.28?Gy, or ET D_max?>?57.23?Gy, the risk of high-frequency CHL in NPC patients increased.

Conclusions and significance: SNHL and CHL remain common ear complications after IMRT for NPC. IAC D_max, IAC D_mean, ME D_max, ME D_mean, and ET D_max all need to be carefully considered during the IMRT treatment protocol.     

Retention of intratumor injections of cisplatinum in murine tumors and the impact on laser thermal therapy for cancer treatment

Recent studies using murine models of human squamous cell carcinoma (SCCA) have revealed a significant improvement in survival and cure rate of animals transplanted with human SCCA when treated with a combination of intratumor injections of chemotherapy and laser induced thermal therapy (LITT). These preliminary results suggest that this novel combination therapy may lead to improved clinical response compared to either treatment modality alone. Using a murine model of human SCCA we investigated two different modes of intratumor injection of cisplatin: a sustained-release cisplatin gel implant (CDDP/gel) versus cisplatin in solution (CDDP) at varying doses (range 1–3 mg/ml). In addition, we tested CDDP/gel combined with LITT. Results showed optimal drug concentration (30–300 nM) at tumor margins up to 4 h after injection of CDDP/gel implant compared to 3 nM at 5 min after injection with CDDP solution. Combined CDDP/gel and laser therapy significantly decreased tumor volume (P < 0.05), with recurrence in only 25% of animals tested, compared to 78% tumor regrowth after LITT alone. These results suggest that laser chemotherapy may be an effective treatment for head and neck SCCA. Presented at the 2005 Annual Meeting of the Academy of Otolaryngology, Head and Neck Surgery. September 26, 2005, Los Angeles, CA, USA.     

A randomized trial of neoadjuvant vs concomitant chemotherapy vs radiotherapy alone in the treatment of stage IV head and neck squamous cell carcinoma

Summary Treatment results of irradiation as a single treatment for advanced stage IV unresectable head and neck cancer remains uniformly poor and apparently has not changed with the most recent improvements in oncological care. Despite several negative results of randomized studies, neoadjuvant or concomitant chemotherapy and radiotherapy seems to improve the number of complete responses and also the duration of disease-free survival. The present study was designed to determine the feasibility, potential risks and benefits of the two methods of combined treatment and radiotherapy alone on the management of advanced unresectable squamous cell carcinoma of the upper respiratory and digestive system. From 1983 to 1986, 90 patients entered the trial. Thirty patients were randomized to each study group: radiotherapy alone (70 Gy); neoadjuvant chemotherapy (vinblastine, mitomycin, cisplatin, and bleomycin) and radiotherapy; concomitant chemotherapy (cisplatin and bleomycin) and radiotherapy. An increased frequency of complete responses (33%) was seen in patients treated with the two different combinations of chemotherapy and irradiation compared to irradiation alone (10%). However, toxicity was more common in patients treated with the two modalities of combined treatment and there were no differences in overall survival rates (P = 0.706).     

Benefits of prophylactic percutaneous gastrostomy in patients with nasopharyngeal cancer receiving concurrent chemoradiotherapy: A multicenter analysis

PurposeProphylactic percutaneous endoscopic gastrostomy (PPEG) is widely used for patients with head and neck cancer undergoing concurrent chemoradiation (CCRT). Nevertheless, the necessity of its use in patients with nasopharyngeal cancer (NPC) is uncertain. This study aimed to evaluate the benefits of PPEG on prevention of weight loss and treatment tolerance in patients with NPC receiving CCRT.Materials and methodsA retrospective multicenter chart review of 904 patients, 378 in the PPEG group and 526 in the non-PPEG group, was conducted. Baseline characteristics, weight loss, and treatment tolerance were analyzed and compared between the two groups.ResultsThere was no significant difference in the mean baseline body mass index (BMI) between the groups. At the end of CCRT, no difference in weight loss was found between the 2 groups (non-PPEG group, 6.6%; PPEG group, 5.9%). Nonetheless, the subgroup analysis demonstrated that a baseline BMI < 18.5 kg/m² (underweight) and non–intensity-modulated radiation therapy (IMRT) technique were independent factors associated with prevention of weight loss by PPEG. More patients in the PPEG group were able to complete planned cycles of chemotherapy (73.3% vs. 49.0%, P < .0001).ConclusionAlthough the benefits of PPEG on prevention of weight loss were not observed for the entire cohort, we found a potentially protective effect of PPEG in some subgroups of patients. Additionally, PPEG significantly enhanced chemotherapy tolerance. Therefore, PPEG tube insertion should be strongly considered for patients with NPC receiving CCRT, particularly for underweight patients and those undergoing a non-IMRT technique.     

Neue Aspekte der prim?ren Radiochemotherapie bei Kopf-Hals-Tumoren

Primary radiochemotherapy is a treatment option for patients with locally advanced or unresectable head and neck cancer. Compared to conventional radiotherapy, intensity-modulated radiotherapy (IMRT) is associated with fewer long-term toxicities and better quality of life. Whether IMRT improves local control in these patients needs to be further investigated. The risk factors and treatment toxicities must be taken into consideration and discussed with the patients. New approaches combining radiotherapy and biological targets are a treatment option. The implementation of these substances in treatment protocols is increasing. Sensitive and specific prognostic biomarkers for patient identification to optimize treatment selection are important, but reliable parameters are still missing.     

Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxane-based induction chemotherapy and concurrent chemo-radiotherapy in the modern era

ObjectiveTo evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension (ICE) treated with induction chemotherapy (ICT) followed by chemo-intensity-modulated radiotherapy (CTRT) at a tertiary cancer center.MethodsWe retrospectively analyzed 45 patients with histologically proven, non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016. Patients were classified as minor ICE or major ICE, based on the extent of ICE. All the patients received 2–3 cycles of a taxane-based ICT regimen followed by CTRT. Radiotherapy was delivered with “risk-adapted” intensity-modulated radiotherapy (IMRT) technique in all patients.ResultsAfter a median follow up of 45 months (range: 8–113 months), the estimated 5-year DFS, LRFS, DMFS, and OS of the entire cohort was 58%, 82%, 67% and 74% respectively. On multivariate analysis, histological subtype was an independent predictor of LRFS, and age was an independent predictor of DFS. The extent of ICE showed only a trend towards worse DFS (P = 0.06). None of the factors significantly predicted for DMFS or OS. Gender, N-stage, and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 22% of patients and grade 2 or worse xerostomia was seen in 24% of patients at last follow up. Thirty-three percent of the patients developed clinical hypothyroidism at last follow up. None of the patients experienced any neurological or vascular complications.ConclusionsTaxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension. Distant metastasis continues to be the predominant problem in these patients.     

Prospective phase II trial of concomitant boost radiotherapy for stage II nasopharyngeal carcinoma: an evaluation of response and toxicity

INTRODUCTION: Stage II nasopharyngeal carcinoma (NPC) treated with conventionally fractionated radiotherapy results in loco-regional control of around 80%. This report aims to document the outcome of Stage II NPC patients treated with external beam radiotherapy delivered using an accelerated concomitant boost (C-Boost) schedule. METHODS AND MATERIALS: Twenty-five 1997 AJCC Stage II NPC patients were enrolled and analyzed in this preliminary report. The primary tumor and clinically involved nodes received a total dose of 72 Gy in 42 fractions. C-Boost for gross disease consisted of 18 Gy in 12 fractions commencing on day 19 and was delivered at least 6 hours after the first dose. Patients were assessed for response, survival, and toxicity. RESULTS: With a median follow-up of 24 months, only one patient had pathologically confirmed local recurrence, necessitating IMRT. Two developed distant metastases for which they received chemotherapy. One died from systemic disease after refusing treatment for persistent neck lymphadenopathy. Two-year loco-regional control rates, overall survival and disease-free survival rates were 96%, 96%, and 88%, respectively. All patients experienced some degree of acute and/or late toxicity. However, the toxicity profile was comparable to that seen following standard fractionation. Acute or late toxicities directly attributable to C-Boost were not observed. CONCLUSION: This C-Boost radiotherapy regimen administers a substantially higher biologically effective dose compared with conventional radiation schedules. Preliminary locoregional control and survival rates are promising with no significant acute and/or late toxicities.     

Evaluation of overall tumor cellularity after neoadjuvant chemotherapy in patient with locally advanced hypopharyngeal cancer

The aim of this study is to clarify the prognostic value of the pathological overall tumor cellularity after neoadjuvant chemotherapy for locally advanced hypopharyngeal cancer. In consecutive series of 45 operable patients with locally advanced hypopharyngeal cancer, neoadjuvant chemotherapy by cisplatin and 5-fluorouracil was administered. Pathological image analysis was performed in 30 patients using the large cross-section specimen after total resection to evaluate the overall tumor cellularity. The chemotherapeutic responses were classified according to the pathological grading scale by dividing into four categories; more than 70% overall tumor cellularity in Grade 1, between an estimated 10 and 70% in Grade 2, less than 10% in Grade 3, and no identifiable malignant tumor cells in Grade 4. The pathological grades were taken into account for analysis of the survival. In 30 available patients, 40% had Grade 1 pathological response, 30% had Grade 2, and 30% had Grade 3. There was no Grade 4 patient. The overall 5-year survival rate for these 30 patients was 53.33%. The survival rate (61.66%) for patients with Grade 2 and 3 responses was significantly higher than that (27.78%) for patients with Grade 1 response (p?=?0.009). Cox regression analysis revealed that the increasing pathological grade was an independent predictor of a better survival in patients undergoing neoadjuvant chemotherapy. We have shown that the prognosis of patients with locally advanced hypopharyngeal cancer, who had been treated by neoadjuvant chemotherapy followed by total resection, can be predicted by evaluation of pathological overall tumor cellularity from the large section specimen.     

Nasopharyngeal carcinoma in a non-endemic country—Validation of the new NPC staging system

BackgroundNasopharyngeal carcinoma (NPC) staging has recently been updated, with the eighth edition of the AJCC/UICC. In the last ten years, Intensity Modulated Radiotherapy (IMRT) has become a standard treatment for NPC. The authors aim to assess the benefits of the new AJCC staging system in predicting prognosis, as well as the improvement in survival outcomes in the IMRT era, in non-edemic population.MethodsRetrospective study selecting patients treated for NPC between January 2009 and December 2019 in a cancer treatment center in Portugal. Initial TNM staging (according to the seventh edition of the AJCC/UICC) was collected and each patient was restaged according to the new TNM staging system. Overall survival (OS) and Distant Metastasis Free Survival (DMFS) stratified by T and N classification and stage (according to the both TNM staging systems) were analyzed. Univariate and multivariate analysis was performed to evaluate which factors influence OS and DMFS. Data in this series was compared with a previous report from the same institution, before IMRT standard use.Results113 patients were included, averaging 53.74 (±1.4) years old. With the new TNM staging, 5 patients were downstaged and 3 patients were upstaged. Over a median follow-up time of 41 months, the 5-year OS and DMFS were 77% and 79.8%, respectively. Neither the seventh nor the eighth editions of the AJCC/UICC staging system had good overall discrimination between each T classification OS and DMFS curves. Both the seventh and the eighth editions of the AJCC/UICC staging system had statistically significant overall discrimination between each N group and each stage group classification OS curves. Only N classification predicted OS in multivariate analysis. When comparing to a previous report from the same institution, OS has not improved majorly, especially in locoregionally advanced disease.ConclusionsTNM staging still presents limitations in adequately predicting OS and DMFS.     

Organ preservation in locally advanced head and neck cancer of the larynx using induction chemotherapy followed by improved radiation schemes

The present prospective study seeks to evaluate overall and disease free survival, response and organ preservation rate, and toxicity of an intensive chemotherapy regimen (CT) followed by unconventional radiotherapy (RT) in patients with locally advanced operable head and neck cancer. Between January 1998 and December 2006 (June 2005), 115 patients with locally advanced, operable head and neck cancer were evaluated. A total of 333 cycles of neoadjuvant CT (cisplatin–5FU, days 1, 14, 28) followed by hyperfractionated/accelerated radiotherapy were given to 108 patients. A total of 108 patients were evaluable and received the planned CT–RT treatment. Two months after the end of RT, 97.2% of patients had a clinical complete remission of the primary and 67.5% of the neck node site. The overall survival was 55% and cause-specific survival was 73% at 5 years. Of the 33 relapsed patients, 12 recurred only at the primary site and 10 patients had distant metastases. The overall organ preservation rate was 73.5%. The chemotherapy regimen reported an overall cardiotoxicity from 5FU in 14% of patients, with severe toxicity in 3%. The radiotherapy schedule developed 84% of Grade 3–4 mucositis in the observed patients. The accelerated CT–RT regimen is able to achieve a high rate of larynx preservation, a good tolerability, and a satisfactory cause-specific overall survival.