Benefits of immunonutrition in patients with head and neck cancer receiving chemoradiation: A phase II randomized, double-blind study.

BACKGROUND & AIMS: The benefits of immunonutrition in patients with head and neck cancer (HNC), especially for those undergoing definitive concurrent chemoradiation (CCRT), remain unclear. We evaluated the benefits of immunonutrition regarding the prevention of severe oral mucositis. Secondary objectives included assessments of other treatment-related toxicities, changes of nutritional and inflammatory marker levels, treatment tolerance, and survival. METHODS: In total, 110 patients with HNC undergoing definitive CCRT including 3-week cycles of cisplatin were enrolled in our double-blind phase II study. Patients were randomly assigned to receive an immunonutrient formula containing omega-3-fatty acids, arginine, dietary nucleotides, and soluble fiber (n = 55) or an isocaloric isonitrogenous control (n = 55). All patients received the assigned product 5 consecutive days before each chemotherapy session. The proportion of patients with severe oral mucositis was compared between the immunonutrients and control groups. RESULTS: The rates of nasopharyngeal cancer (NPC) were 67% and 51% in the immunonutrients and control groups, respectively. All patients had 100% compliance to the assigned product. There was no difference of the proportion of patients with grade 3-4 oral mucositis between the two groups (62% vs. 67%, p = 0.690). At the time of analyses, survival tended to be better in the immunonutrients group. The 3-year progression-free survival rates were 69% (95% confidence interval [CI] = 55%-80%) and 44% (95% CI = 30%-57%) in the immunonutrients and control groups, respectively (p = 0.056), whereas the 3-year overall survival rates in these groups were 69% (95% CI = 54%-80%) and 50% (95% CI = 36%-66%; p = 0.065), respectively. In subgroup analyses according to the primary tumor location, the survival benefits were apparently maintained in patients with NPC. CONCLUSIONS: Although our study did not demonstrate a reduced risk of severe oral mucositis, we found that immunonutrition might improve survival. Larger studies are needed to determine the optimal dose and schedule of immunonutrition to prevent oral mucositis. In addition, randomized phase III trials evaluating the survival benefits of immunonutrition in patients with cancer are required, and NPC might be a primary malignancy of interest. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05101889.

Efficacy of induction chemotherapy combined with chrono-chemotherapy and intensity-modulated radiotherapy on locally advanced nasopharyngeal carcinoma.

PURPOSE: The purpose of this study was to compare the efficacy and safety of induction chemotherapy combined with chrono-chemotherapy or conventional chemotherapy and intensity-modulated radiotherapy (IMRT) in locally advanced nasopharyngeal carcinoma. METHODS: 150 patients with locally advanced nasopharyngeal carcinoma were divided into two groups: chrono-chemotherapy group (n=75, receiving induction chemotherapy combined with chrono-chemotherapy and IMRT, and control group (n=75, receiving induction chemotherapy combined with conventional chemotherapy and IMRT. Besides, the levels of T lymphocyte subsets in peripheral blood before and after treatment were compared, and the long-term survival and disease progression were followed up and recorded. RESULTS: After treatment, the short-term efficacy of patients was evaluated. The overall response rate was 94.7% (71/75) in chrono-chemotherapy group and 96.0% (72/75) in control group. Moreover, the levels of cluster of differentiation (CD)3+, CD4+, CD8+, CD4+/CD8+, CD16+CD56+ and CD19+ T cells in peripheral blood of patients at 6 months after treatment were significantly lower than those before treatment. The level of posttreatment CD16+CD56+ T cells in chrono-chemotherapy group was significantly higher than that in control group. Furthermore, the follow-up results showed that the 3-year overall survival (OS) was 73.3% and 69.3%, and the 3-year progression-free survival (PFS) was 60.0% and 62.7% in chrono-chemotherapy group and control group, respectively. Finally, Log-rank test showed no significant differences in OS and PFS between the two groups of patients. CONCLUSIONS: As a new treatment mode, chrono-chemotherapy combined with induction chemotherapy and IMRT can reduce the incidence rate and severity of treatment-related adverse reactions and improve immunosuppression without reducing clinical efficacy, which is worthy of clinical promotion and application.

Association of tumor downstaging after neoadjuvant chemotherapy with survival in patients with locally advanced nasopharyngeal carcinoma: a retrospective cohort study.

PURPOSE: Assessing the downstaging effects of neoadjuvant chemotherapy (NACT) in patients with locally advanced nasopharyngeal carcinoma (LANPC) and predicting response to treatment remain challenging. The present study aimed to evaluate the long-term prognosis of downstaging after NACT in patients with LANPC and to investigate the prognostic value of post-NACT tumor downstaging on treatment outcomes in the era of concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included 226 patients with stage III (n = 188) and IVA (n = 38) NPC admitted to Haikou People's Hospital between 1 October 2009 and 1 October 2012. The patients were grouped as downstaging or no after NACT. Overall survival (OS), locoregional failure-free survival (LFFS), and distant failure-free survival (DFFS) were analyzed. RESULTS: Among 226 patients, 196 (86.7%) were in the downstaging group and 30 (13.3%) were in the non-downstaging group. The longest follow-up was 76 months, and the median was 45 months. The 3-year OS rates of the downstaging group and non-downstaging group were 91.0% (95% CI 0.89-0.93) and 69.5% (95% CI 0.66-0.72) (P = 0.005). The 5-year OS rates were 81.6% (95% CI 0.78-0.86) and 53.3% (95% CI 0.49-0.61) (P = 0.001). N downstaging (3-year OS, HR 0.491, 95% CI 0.221-0.881, P = 0.022; 5-year OS, HR = 0.597, 95% CI 0.378-0.878, P = 0.021) was independently associated with OS. CONCLUSION: In the treatment of LANPC, the patients with downstaging after NACT have a better prognosis than those without downstaging. This study suggests that NACT can improve the prognosis for patients with LANPC if there is downstaging.

Survival benefit of induction chemotherapy for locally advanced nasopharyngeal carcinoma: prognosis based on a new risk estimation model.

BACKGROUND: Although the National Comprehensive Cancer Network (NCCN) Guidelines recommend CCRT+AC and IC + CCRT as level 2A evidence for treatment of the locoregionally advanced NPC (II-IVa), IC + CCRT+AC could also be an alternative but it is seldom used because of the low completion rates. This article aimed to compare the effectiveness of the three radiotherapy regimens using a large-scale retrospective study. METHODS: This retrospective single center analysis enrolled 1812 diagnosed NPC patients at Nanfang Hospital from January 2005 to December 2015 and only 729 patients met the inclusion criteria and were analyzed. Patients without distant metastasis, age of 18-70 years, Karnofsky scores of at least 70,stage III-IVb, and adequate adequate bone marrow, liver and renal function. Were enrolled. Adverse events and other categorical variables were compared by Pearson chi-square test or Fishier exact test. Time-to-event data were described with the Kaplan-Meier curves, time-to-event intervals compared with the log-rank test. We did multivariable analyses with the Cox proportional hazards model to test the independent signifi cance of diff erent factors. Cox proportional hazards model was used to estimate the ß regression coeffi cient, p value, and hazard ratio and its 95% CI for each of the selected risk predictors. RESULTS: The median follow-up time was 47 months. Kaplan-Meier analyses revealed no significant differences among three groups in 3-year failure-free survival (FFS, P = 0.225), 3-year overall survival (OS, P = 0.992), 3-year locoregional failure-free survival (LFFS, P = 0.549), and 3-year distant failure-free survival (DFFS, P = 0.174). Stratified survival analysis based on the risk scoring model revealed no differences in FFS, OS, LFFS, and DFFS between IC + CCRT and CCRT+AC groups for low-risk patients, however, the 3-year OS (88.3% vs. 77.6%, P = 0.049) and 3-year DFFS (84.0% vs.66.8%, P = 0.032) were respectively significantly better in IC + CCRT group compared with CCRT+AC group for high-risk patients. CONCLUSIONS: Compared with CCRT+AC, IC + CCRT lowers distant metastasis rate and improves OS among patients with locally advanced NPC in high risk group.

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement.

BACKGROUND & AIM: Several studies explored the association of vitamin B6 intake with the risk of cancers. However, it is unclear whether different doses of vitamin B6 have distinct effects on the prognosis of nasopharyngeal carcinoma (NPC) patients. This study investigated the relationship between different doses of B6 intake and the prognosis of NPC patients. METHODS: This retrospective cohort analysis included 792 newly diagnosed NPC patients with a median follow-up of 62.05 months. Restricted cubic spline and maximally selected rank statistics were performed to determine the cut-off value of vitamin B6 during treatment (VB6DT). Kaplan-Meier method and log-rank tests were performed to analyze survival outcomes. A multivariable Cox proportional hazard model was performed to determine the independent prognostic factors. RESULTS: NPC patients were divided into three groups according to the cut-off value of VB6DT: non-users (0 mg/d), VB6DT > 8.6 mg/d, and VB6DT ≤ 8.6 mg/d. Patients with VB6DT > 8.6 mg/d had significantly lower 5-year overall survival (OS) (83.5% vs. 90.8%, p = 0.006), distant metastasis-free survival (DMFS) (83.5% vs. 91.0%, p = 0.004), and progression-free survival (PFS) (73.7% vs. 81.7%, p = 0.011) and slightly but not significantly lower 5-year local recurrence-free survival (LRFS) (87.7% vs. 90.7%, p = 0.214) than the non-users. Patients with VB6DT ≤ 8.6 mg/d had slightly but not significantly better 5-year OS (93.3% vs. 90.8%, p = 0.283) than the non-users, while all other primary endpoints were similar (p > 0.50). Multivariable analyses confirmed that VB6DT > 8.6 mg/d was an independent negative prognostic factor of OS (p = 0.010), DMFS (p = 0.017), and PFS (p = 0.030) but not of LRFS (p = 0.428). CONCLUSIONS: Excessive VB6DT higher than the cut-off value is an independent negative prognostic factor for NPC patients. Additionally, low dose intake improved OS only slightly but not significantly.

Short-term outcomes of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (TPF) in locally advanced nasopharyngeal carcinoma.

There is an unmet need for improving survival outcomes of locally advanced nasopharyngeal carcinoma, for example, T4/ N3 stage disease. To this end, we administered induction chemotherapy (IC) with TPF (docetaxel, cisplatin, and fluorouracil) because this stage of disease is associated with a high risk of recurrence and is difficult to control with standard treatments, such as chemoradiotherapy (CRT) alone or CRT followed by adjuvant chemotherapy. The aim of this retrospective single-center study was to clarify the short-term outcomes of locally far-advanced nasopharyngeal carcinoma patients treated with IC-TPF, followed by CRT with cisplatin. Data from 11 patients were extracted from our database, indicating that the overall response rate to IC-TPF, clinical complete response rate after CRT, 1-year progression-free survival, and 1-year overall survival were 73%, 91%, 68%, and 89%, respectively. Hematological toxicity was the most common adverse event reported during IC-TPF with 64% of patients suffering grade 3 or 4 neutropenia, 55% grade 3 or 4 leucopenia and 9% febrile neutropenia. Despite the small number of patients, these data are important because there is a limited number of studies investigating IC-TPF followed by CRT in Japanese patients. This pilot study provides some indication of the short-term effectiveness and toxicity of this therapeutic approach, which may be superior to standard treatments. Long-term follow-up is warranted to assess the effectiveness of IC-TPF in terms of clinical outcome and late-phase toxicity.

Adjunctive Chinese herbal medicine therapy for nasopharyngeal carcinoma: Clinical evidence and experimental validation.

BACKGROUND: To investigate the benefits of adjunctive Chinese herbal medicine (CHM) for patients with nasopharyngeal carcinoma (NPC). METHODS: We included all patients diagnosed with NPC during 1997-2009 and followed until 2011 in Taiwan. We used 1:1 frequency matching by age, sex, comorbidity, conventional treatment, and index year to compare the CHM users and non-CHM users (n = 2542 each). The prescribed CHM was further investigated with regard to its cytotoxicity. RESULTS: Compared with non-CHM users, adjunctive CHM users had a lower hazard ratio of mortality risk, and a better survival probability. Gan-Lu-Yin (GLY) was the most commonly prescribed CHM, and it reduced cell viability, inhibited tumor proliferation, and induced apoptosis through the poly (ADP-ribose) polymerase and caspase-3-dependent pathway in human NPC TW01 cells. Oral administration of GLY retarded NPC-TW01 tumor growth in the xenograft nude mouse model. CONCLUSION: Real-world data and laboratory experiments implied that adjunctive CHM might be beneficial for NPC patients.

Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with cisplatin and 5-fluorouracil in patients with metastatic nasopharyngeal carcinoma after radical radiotherapy: a multicentre, open-label, phase II clinical trial.

BACKGROUND: We conducted a single-arm phase II trial to evaluate the efficacy and adverse effects (AEs) of an anti-epidermal growth factor receptor monoclonal antibody, nimotuzumab, combined with cisplatin and 5-fluorouracil (PF) as first-line treatment in recurrent metastatic nasopharyngeal carcinoma after radical radiotherapy. METHODS: Patients who met the eligibility criteria were recruited from ten institutions (ClinicalTrials.gov; NCT01616849). A Simon optimal two-stage design was used to calculate the sample size. All patients received weekly nimotuzumab (200 mg) added to cisplatin (100 mg/m2 D1) and 5-fluorouracil (4 g/m2 continuous infusion D1-4) every 3-weekly for a maximum of six cycles. Primary end point was objective response rate (ORR). Secondary end points included disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and AEs. RESULTS: A total of 35 patients were enrolled (13 in stage 1 and 22 in stage 2). Overall ORR and DCR were 71.4% (25/35) and 85.7% (30/35), respectively. Median PFS and OS were 7.0 (95% CI 5.8-8.2) months and 16.3 (95% CI 11.4-21.3) months, respectively. Unplanned exploratory analyses suggest that patients who received ≥2400 mg nimotuzumab and ≥4 cycles of PF had superior ORR, PFS and OS than those who did not (88.9% versus 12.5%, P < 0.001; 7.4 versus 2.7 months, P = 0.081; 17.0 versus 8.0 months, P = 0.202). Favourable subgroups included patients with lung metastasis [HROS 0.324 (95% CI 0.146-0.717), P = 0.008] and disease-free interval of >12 months [HROS 0.307 (95% CI 0.131-0.724), P = 0.004], but no difference was observed for metastatic burden. The only major grade 3/4 AE was leukopenia (62.9%). CONCLUSION: Combination nimotuzumab-PF chemotherapy demonstrates potential efficacy, and is well tolerated as first-line chemotherapy regimen in recurrent metastatic nasopharyngeal carcinoma.

Impact of different therapeutic regimens on survival of patients with nasopharyngeal carcinoma.

PURPOSE: Nasopharyngeal carcinoma (NPC) demonstrates specific histo-genetic features that affect its biological behaviour. Our aim was to investigate the correlation between different therapeutic approaches and survival of patients with NPC in southwestern Greece based on specific clinicopathological features. METHODS: Seventy-two NPC patients (n=72) were treated between 1990 and 2014 at the University Hospital of Patras. Patient demographics, tumor histology, use of tobacco and alcohol, exposure to mutagenic agents, chosen treatment and survival were recorded. All patients were treated with radiotherapy (RT), chemotherapy, surgery or their combinations. RESULTS: In the patients who used immobilization mask during RT, the 5-year survival rate and overall survival was higher than the rest of patients (57% and 6 years vs. 13.6% and 3.36 years, p=0.0001, respectively)*. RT with mask combined with chemotherapy increased survival rates compared to RT without chemotherapy conventional regimen (p=0.0001). Additionally, patients who received chemotherapy demonstrated a 5-year survival of 51.6% compared to those without chemotherapy (11% p=0.0014). (*The 5-year survival rate group of patients refers to the percentage of people who will be alive 5 years after diagnosis. It does not include those who die from other diseases. Sometimes, this includes all people with a specific cancer type. Researchers call this an overall rate. In contrast, overall survival provides information for the length of time from either the date of diagnosis or the start of treatment for a disease, such as cancer, that patients diagnosed with the disease are still alive. In a clinical trial, measuring the overall survival is one way to see how well a new treatment works.) Conclusions: In the majority of examined NPC cases treated with the use of immobilization RT mask along with chemotherapy, a significantly better prognosis compared to conventional RT-chemotherapy treatment was observed. Thus, chemotherapy offers an advantage to patient survival as an adjuvant treatment regimen in conjunction with RT.

Concurrent chemoradiotherapy by simultaneously integrated boost volumetric-modulated arc therapy for nasopharyngeal carcinoma-toxicity/quality of life and survival.

BACKGROUND: To investigate the toxicity, changes of quality of life (QOL), and survival for patients with nasopharyngeal cancer (NPC) treated by concurrent chemoradiotherapy (CCRT) with simultaneously integrated boost volumetric-modulated arc therapy (SIB-VMAT). METHODS: A total of 68 NPC patients treated by CCRT with SIB-VMAT technique were collected. QOL was longitudinally assessed by the EORTC QLQ-C30 and HN35 questionnaires at the 4 time points: baseline, 42.4 Gy (20 fractions), and 3, 12 months after CCRT. RESULTS: The 4-year locoregional relapse free, distant metastasis free, failure free, and overall survival rates were 97.0%, 86.4%, 82.0%, and 88.1%, respectively. The 4-year cumulative incidence rate of late toxicities with grade 3 or more was 3.0%. One year after CCRT, most QOL scales, except some oral related symptoms, recovered to baseline level. CONCLUSION: CCRT with SIB-VMAT produces excellent locoregional control, few severe late toxicity, and good general health status for NPC patients.

Which neoadjuvant chemotherapy regimen should be recommended for patients with advanced nasopharyngeal carcinoma?: A network meta-analysis.

BACKGROUND: The clinical application has widespread disagreement on the different regimens of neoadjuvant chemotherapy (NCT) in the treatment of locoregionally advanced nasopharyngeal carcinoma (NPC). We conducted a network meta-analysis (NMA) to evaluate the efficacy of the different NCT regimens in the treatment of NPC. METHODS: A systematic literature search was performed using PubMed, Embase, and Cochran Library. Totally, 31 randomized controlled trials (RCTs) (n = 4062) met study selection criteria and were incorporated in this NMA study. RESULTS: Our study showed that certain NCT regimens improved the prognosis of patients, and found out the relative best solution for each endpoint, such as paclitaxel, carboplatin, and gemcitabine for 1-year overall survival (OS) rate, cisplatin, calcium folinate, and 5-fluorouracil for 2-year OS rate, vinorelbine and cisplatin (NP) for 3-year OS rate, cyclophosphamide, cisplatin, and 5-fluorouracil for 5-year OS rate, NP for complete remission rate, cisplatin and gemcitabine for overall remission rate of the primary tumor. In addition, for certain grade 3 and above toxicity, the results of the NMA reflected certain NCT regimens can reduce toxicity of chemoradiotherapy (CRT) to a minimum, such as NP for anemia, mucositis, and thrombocytopenia, paclitaxel, epirubicin, and cisplatin for neutropenia and skin toxicity. CONCLUSION: Our NMA showed that certain cisplatin-based NCT regimens improved the prognosis of patients with NPC and reduced the toxicity of CRT. However, in view of survival rate and response rate, the best NCT regimen is not entirely consistent. Therefore, which NCT regimen will benefit most patients will need further explored.

Survival without adjuvant chemotherapy for selected patients with stage II and III nasopharyngeal carcinoma after concurrent chemoradiotherapy alone.

BACKGROUND: The role of adjuvant chemotherapy after concurrent chemoradiotherapy (CRT) for nasopharyngeal carcinoma (NPC) is controversial. We report our phase II prospective study of withholding adjuvant chemotherapy in a subgroup of patients with American Joint Committee on Cancer (AJCC) stage II and III NPC with low risk for metastasis. METHODS: Between April 1998 and December 2008, 263 patients with stage II (AJCC 1997 T2aN0, T1-T2aN1; AJCC 2010 T1N1) NPC or stage III (AJCC 1997 T1-T2aN2; AJCC 2010 T1N2) NPC were enrolled. Patients received standard concurrent CRT with cisplatin and 5-fluorouracil (5-FU) but without adjuvant chemotherapy. RESULTS: With a median follow-up of 107 months, the 5-year overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were 92.4%, 84.4%, and 90.7% for all patients; 94.1%, 85.9%, and 92.9% for patients with stage II NPC; and 90.9%, 83.2%, and 88.9% for patients with stage III NPC, respectively. CONCLUSION: It is safe to withhold adjuvant chemotherapy for selected patients with stage II and III NPC.

[Neoadjuvant chemotherapy with concurrent chemoradiotherapy in the treatment of nasopharyngeal cancer: Southern Tunisian experience]. / La chimiothérapie néoadjuvante associée à la chimioradiothérapie concomitante dans le traitement du cancer du nasopharynx : expérience du Sud-Tunisien.

PURPOSE: A retrospective study to evaluate the efficacy and safety of the addition of neoadjuvant chemotherapy to concurrent chemoradiotherapy in the treatment of nasopharyngeal carcinoma. PATIENTS AND METHODS: Data from 62 patients treated for non-metastatic nasopharyngeal carcinoma were analyzed by comparing two groups of patients: a first group of 32 patients treated with 3 cycles of neoadjuvant chemotherapy based on docetaxel, cisplatin and 5-fluoro-uracil every 21 days followed by concurrent chemoradiotherapy (weekly cisplatin 40mg/m2 with radiotherapy 70Gy, 2Gy per session, 5 sessions per week) and a second group of 30 patients treated with the same concurrent chemoradiotherapy. RESULTS: After a median follow-up of 53.5 months, neoadjuvant chemotherapy showed a significant reduction in the rate of a distant metastatic relapses (3.3% vs. 10%, P=0.03). No significant difference in disease-free survival at 5 years (65.6% vs. 68.8%, P=0.46) or overall survival at 5 years (68.8% vs. 73.3%, P=0.46) was noted between the two groups. Induction chemotherapy was associated with febrile neutropenia of 15.6%. During concurrent chemoradiotherapy, hematological complications were greater in the first chemotherapy group (53% vs. 33%). CONCLUSION: Induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil is a safe and effective option in the treatment of nasopharyngeal carcinoma. A better definition of high risk of relapse group would optimize the indications of this chemotherapy in the therapeutic arsenal.

Refining the Role of Lymph Node Biopsy in Survival for Patients with Nasopharyngeal Carcinoma: Population-Based Study from the Surveillance Epidemiology and End-Results Registry.

BACKGROUND: The updated version of the National Comprehensive Cancer Network (NCCN) guidelines revised pretreatment workup for nasopharyngeal carcinoma (NPC) into "biopsy of the primary site or neck." Despite provision of important diagnostic information, concerns regarding tumor cell dissemination limit the application of lymph node biopsy. This study aimed to investigate whether biopsy of the neck is associated with impaired survival in NPC. METHODS: A propensity score-matched, population-based cohort identified from the Surveillance, Epidemiology, and End Results database was used to compare overall survival (OS) and disease-specific survival (DSS) of patients who underwent pretreatment cervical lymph node biopsy without subsequent neck dissection or removal of node compared with patients who did not undergo node biopsy. RESULTS: Of 2910 eligible patients, 416 (14.3%) underwent pretreatment lymph node biopsy. After use of control for patient, tumor, and demographic characteristics, biopsy was not associated with impaired OS (hazard ratio [HR], 1.15; 95% confidence interval [CI] 0.89-1.47; P = 0.29) or DSS (HR, 1.07; 95% CI 0.81-1.40; P = 0.63). Interestingly, in the subgroup analysis, the unfavorable effect of biopsy was observed for patients with differentiated non-keratinizing squamous cell carcinoma (but not other histologic types). Race did not positively alter the survival outcomes. CONCLUSIONS: The findings provide reference for clinical practice, showing that pretreatment cervical lymph node biopsy is not associated with impaired survival in NPC, except for patients with differentiated non-keratinizing squamous cell carcinoma. The recommended NCCN guidelines would be more specific by adding details to the general recommendation that neck biopsy is safe for all patients. Future prospective studies are needed to verify the study findings.

A multicenter, phase 3, randomized trial of concurrent chemoradiotherapy plus adjuvant chemotherapy versus radiotherapy alone in patients with regionally advanced nasopharyngeal carcinoma: 10-year outcomes for efficacy and toxicity.

BACKGROUND: Concurrent-adjuvant chemoradiotherapy (CRT) became a recommended treatment for locoregionally advanced nasopharyngeal carcinoma (NPC) with the first report of a significant survival benefit from the Intergroup 0099 study. However, data on late toxicities are lacking. Previous reports from the current NPC-9901 trial have raised concerns about a failure to improve overall survival (OS) because of an inadequate impact on distant control and increases in toxicities/noncancer deaths. Validation of the long-term therapeutic ratio is needed. METHODS: In this phase 3, randomized trial, patients with nonkeratinizing NPC (stage T1-4/N2-3/M0) were randomly assigned to radiotherapy alone (176 patients) or to CRT (172 patients) with concurrent cisplatin followed by adjuvant cisplatin plus fluorouracil. RESULTS: The early findings of significant improvements in tumor control were maintained: the CRT group achieved significantly higher 10-year overall failure-free (62% vs 50%; P = .01) and progression-free survival rates (56% vs 42%; P = .006) because of superior locoregional control (87% vs 74%; P = .003), whereas the impact on distant control remained insignificant (68% vs 65%; P = .24). The initial differences in toxicities diminished with longer follow-up: 52% versus 47% at 10 years for late toxicities (P = .20), 4.1% versus 2.8% for deaths due to treatment toxicity, and 15.1% versus 13.1% for deaths due to incidental/unknown causes. The OS rate for the CRT group reached statistical superiority at 10 years (62% vs 49%; P = .047). CONCLUSIONS: Long-term results have confirmed that CRT can significantly improve OS without excessive late toxicities for patients with regionally advanced NPC. However, more potent therapy is needed for improving distant control, especially for patients with stage IVA/B disease. Cancer 2017;123:4147-4157. © 2017 American Cancer Society.

The value of the Prognostic Nutritional Index (PNI) in predicting outcomes and guiding the treatment strategy of nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT) with or without chemotherapy.

PURPOSE: The purpose of this study was to investigate the significance of the Prognostic Nutritional Index (PNI) in predicting prognoses and guiding treatment choices of nasopharyngeal carcinoma (NPC) patients receiving intensity-modulated radiotherapy (IMRT). METHODS: The 539 patients with newly diagnosed non-metastatic NPC were retrospectively analysed. The PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). All patients were split randomly into a training set and a testing set. Receiver operating characteristic (ROC) curves were used to identify the cut-off value of PNI and test its prognostic validity. Survival curves were calculated by Kaplan-Meier method, and differences were compared with log-rank test. RESULTS: The median follow-up time was 109.5 months. The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-specific survival (DSS) and overall survival (OS) of the whole cohort were 90.6, 85.8, 85.3 and 82.7%, respectively. The PNI cut-off value was 52.0 in the training set, which was significant in predicting DMFS, DSS and OS in the testing set. According to the PNI cut-off value, 220 patients of II-IVb stage treated by concurrent chemoradiotherapy (CCRT) were classified into PNI ≤ 52.0 and >52.0 groups and the 5-year LRRFS, DMFS, DSS, and OS of PNI ≤ 52.0 group were significantly worse than the PNI > 52.0 group. CONCLUSION: Our results suggest that the PNI is a reliable independent prognostic factor in NPC patients treated with IMRT. For stage II-IVb patients with PNI ≤ 52.0, CCRT alone does not achieve satisfactory outcomes, and further studies on treatment optimization are needed.

Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial.

AIM OF THE STUDY: Previous results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). METHODS: Patients with stage III-IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m2 and fluorouracil 800 mg/m2/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. RESULTS: Two hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64-1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3-4 toxicities (p = 0.14). CONCLUSION: Adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. REGISTRATION NUMBER: NCT00677118.

Morning breathing exercises prolong lifespan by improving hyperventilation in people living with respiratory cancer.

Disturbance of oxygen-carbon dioxide homeostasis has an impact on cancer. Little is known about the effect of breath training on cancer patients. Here we report our 10-year experience with morning breathing exercises (MBE) in peer-support programs for cancer survivors.We performed a cohort study to investigate long-term surviving patients with lung cancer (LC) and nasopharyngeal cancer (NPC) who practiced MBE on a daily basis. End-tidal breath holding time (ETBHT) after MBE was measured to reflect improvement in alveolar O2 pressure and alveolar CO2 pressure capacity.Patients (female, 57) with a diagnosis of LC (90 patients) and NPC (32 patients) were included. Seventy-six of them were MBE trainees. Average survival years were higher in MBE trainees (9.8 ±â€Š9.5) than nontrainees (3.3 ±â€Š2.8). The 5-year survival rate was 56.6% for MBE trainees and 19.6% for nontrainees (RR = 5.371, 95% CI = 2.271-12.636, P < 0.001). Survival probability of the trainees further increased 17.9-fold for the 10-year survival rate. Compared with the nontrainees, the MBE trainees shows no significant differences in ETBHT (baseline, P = 0.795; 1-2 years, P = 0.301; 3-4 years, P = 0.059) at baseline and within the first 4 years. From the 5th year onwards, significant improvements were observed in ETBHT, aCO2%, PaCO2, and PaO2 (P = 0.028). In total, 18 trainees (40.9%) and 20 nontrainees (74.1%) developed new metastasis (RR = 0.315, 95% CI = 0.108-0.919, P = 0.031).MBE might benefit for the long-term survival in patients with LC and NPC due to improvement in hyperventilation.

Receipt of Care Discordant with Practice Guidelines is Associated with Compromised Overall Survival in Nasopharyngeal Carcinoma.

AIMS: It is unknown whether receiving treatment that is discordant with practice guidelines is associated with improved survival in patients with nasopharyngeal carcinoma. The objectives of this study were to characterise national treatment patterns, analyse whether treatment outside of practice guidelines is associated with overall survival, and identify variables associated with receiving guidelines-discordant care in the USA. MATERIALS AND METHODS: This was a retrospective cohort study of 1741 nasopharyngeal carcinoma patients in the National Cancer Data Base (2003-2006). Treatment regimens were compared with the 2004-2006 National Comprehensive Cancer Network guidelines. Statistical analyses included chi-square, Kaplan-Meier, multivariable logistic, and Cox regression. RESULTS: Nearly 26% of our cohort received care discordant with practice guidelines. In multivariable analysis, patients with stage IVC disease (odds ratio 2.59, 95% confidence interval 1.66-4.04) were more likely to receive guidelines-discordant care when compared with those with stage II-IVB disease. The most common treatment deviation for those with stage I disease was overtreatment with chemoradiation therapy. Receiving guidelines-discordant care was associated with an increased risk of death (hazard ratio 1.46, 95% confidence interval 1.25-1.69). CONCLUSIONS: Many patients with stages I and IVC nasopharyngeal carcinoma do not receive care in accordance with practice guidelines. Receiving guidelines-discordant care is associated with compromised overall survival in the USA.