Neoadjuvant chemotherapy with different dose regimens of docetaxel, cisplatin and fluorouracil (TPF) for locoregionally advanced nasopharyngeal carcinoma: a retrospective study.

OBJECTIVE: Compare high- vs. low-dose TPF neoadjuvant chemotherapy with chemoradiotherapy in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Retrospective analysis of 210 stage III/IV NPC patients treated between April 1, 2012 and April 1, 2014; 138 received three cycles of high-dose TPF (H-TPF) every 3 weeks at Zhejiang Cancer Hospital and 72, three cycles of low-dose TPF (L-TPF) every 3 weeks at Sun Yat-Sen University Cancer Center. H-TPF was docetaxel (75 mg/m2; 1 h infusion), cisplatin (75 mg/m2; 0.5-3 h), then 5-fluorouracil (600 mg/m2/day; 4 days). L-TPF was docetaxel (60 mg/m2), cisplatin (65 mg/m2), then 5-fluorouracil (550 mg/m2/day; 5 days). All patients received chemoradiotherapy. RESULTS: During neoadjuvant chemotherapy, treatment delays were more frequent for H-TPF than L-TPF (33.3% vs. 19.4%; P = 0.034). During chemoradiotherapy, grade III-IV anemia, thrombocytopenia and neutropenia were more common for H-TPF than L-TPF (P < 0.001, P < 0.001, P = 0.048). Fewer patients in the H-TPF group finished two cycles of concurrent chemotherapy (81.2% vs. 100%, P < 0.001). Three-year PFS (84.5% vs. 80.6%, P = 0.484) and OS (91.1% vs. 93.5%, P = 0.542) were not significantly different between H-TPF and L-TPF. CONCLUSIONS: L-TPF neoadjuvant chemotherapy has substantially better tolerance and compliance rates and similar treatment efficacy to H-TPF neoadjuvant chemotherapy in locoregionally-advanced NPC.

High-risk factors of parotid lymph node metastasis in nasopharyngeal carcinoma: a case-control study.

BACKGROUND: Although parotid-sparing IMRT decreased the dose distribution of parotid, parotid region recurrence has been reported. Prophylactic irradiation in parotid area would be necessary in patients with high risk of parotid lymph node metastasis (PLNM). This study was to detect the high-risk factors of PLNM in nasopharyngeal carcinoma. METHODS: This was a 1:2 case-control study. All patients in this study were newly diagnosed NPC with N2-3 classification from January 2005 to December 2012. Cases were 22 sides with ipsilateral PLNM. Controls were 44 patients who were randomly selected from N2-3 disease in database. RESULTS: 20/1096 (1.82 %) NPC patients were found PLNM. Sum of the longest diameter for multiple lymph nodes (SLD) in level II was larger in case group than that in control group (6.0 cm vs. 3.6 cm, p = 0.003). Level II lymph node necrosis, level Va/b involvement, and rare neck areas involvement were more common in case group (p = 0.016, p = 0.034, and p < 0.001, respectively). RPN, level III, and level IV metastases showed no significant difference between the two groups. Multivariate analysis in logistic regression showed that only SLD ≥5 cm in II area (OR = 4.11, p = 0.030) and rare neck areas involvement (OR = 3.95, p = 0.045) were associated with PLNM in NPC patients. CONCLUSIONS: PLNM was an uncommon event in NPC patients. SLD ≥5 cm in level II and involvement in rare-neck areas may be potentially high-risk factors for PLNM. Sparing parotid in IMRT was not recommended for NPC patients with high risks of PLNM.

Intensity-modulated radiotherapy for cervical esophageal squamous cell carcinoma: clinical outcomes and patterns of failure.

The objective of the study was to report clinical outcomes and patterns of failure for these patients with cervical esophageal squamous cell carcinoma (CESCC) treated with intensity-modulated radiotherapy (IMRT). A total of 64 patients with CESCC treated with definitive IMRT from May 2005 to March 2012 in our center were analyzed. Forty-two patients received radiotherapy alone and 22 patients received concurrent chemoradiotherapy. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. For all patients, the overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 74.5, 88.0, 66.6 and 42.5 %, respectively. Twenty-eight patients had developed treatment failure. Of the 28 patients, 14, 5, and 18 had developed local failure, regional failure, and distant metastasis, respectively. All of the 14 local failures were considered in-field failures. Of the five regional failures, three were considered in-field failures and two were marginal failures. The most frequently observed acute toxicity was mainly Grade 1 or 2. The incidence of acute Grade 3 mucositis (including pharyngitis), skin reaction, and leukopenia was 4.7, 12.5 and 10.9 %, respectively. IMRT provides satisfactory locoregional control for CESCC. Distant metastasis remains the predominate pattern of failure and the predominate pattern of locoregional failures is in-field failure.

Nasopharyngeal carcinoma with intracranial extension in the era of intensity-modulated radiotherapy: case-control study using propensity score matching method.

The objective of the study was to evaluate long-term survival outcomes and toxicity of T4 classification nasopharyngeal carcinoma (NPC) with intracranial extension (IE group) or without intracranial extension (non-IE group) after intensity-modulated radiotherapy (IMRT) using the propensity score matching method. After generating propensity scores given the covariates of age, sex, N classification, and concurrent chemotherapy, 132 patients in each group were matched. The 5-year local failure-free survival rate and the 5-year overall survival rate in the IE group were lower than the patients in the non-IE group (74.6 vs. 88.9 %, p = .008; 51.1 vs. 71.9 %, p = .005). Grade 2 hypothyroidism was more common in the IE group (13.2 vs. 3.4 %, p = .029). For patients with T4 classification NPC after IMRT, patients with intracranial extension need more attention to the thyroid gland function and are more likely to experience local failure and death than patients without intracranial extension.

Concurrent chemotherapy for T4 classification nasopharyngeal carcinoma in the era of intensity-modulated radiotherapy.

OBJECTIVE: To evaluate concurrent chemotherapy for T4 classification nasopharyngeal carcinoma (NPC) treated by intensity-modulated radiotherapy (IMRT). METHODS: From July 2004 to June 2011, 180 non-metastatic T4 classification NPC patients were retrospectively analyzed. Of these patients, 117 patients were treated by concurrent chemoradiotherapy (CCRT) using IMRT and 63 cases were treated by IMRT alone. RESULTS: The median follow-up time was 58.97 months (range, 2.79-114.92) months. For all the patients, the 1, 3 and 5-year local failure-free survival (LFFS) rates were 97.7%, 89.2% and 85.9%, regional failure free survival (RFFS) rates were 98.9%, 94.4% and 94.4%, distant failure-free survival (DFFS) rates were 89.7%, 79.9% and 76.2%, and overall survival (OS) rates were 92.7%, 78.9% and 65.3%, respectively. No statistically significant difference was observed in LFFS, RFFS, DFFS and OS between the CCRT group and the IMRT alone group. No statistically significant difference was observed in acute toxicity except leukopenia (p = 0.000) during IMRT between the CCRT group and the IMRT alone group. CONCLUSION: IMRT alone for T4 classification NPC achieved similar treatment outcomes in terms of disease local control and overall survival as compared to concurrent chemotherapy plus IMRT. However, this is a retrospective study with a limited number of patients, such results need further investigation in a prospective randomized clinical trial.

Update report of T4 classification nasopharyngeal carcinoma after intensity-modulated radiotherapy: an analysis of survival and treatment toxicities.

OBJECTIVE: To evaluate the long-term survival outcomes and toxicity of a larger series of patients with non-metastatic T4 classification nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS: From March 2004 to June 2011, 335 non-metastatic T4 classification NPC patients treated by IMRT were analyzed retrospectively. Treatment induced toxicities were scored according to the Common Terminology Criteria for Adverse Events version 3.0. RESULTS: With a median follow-up time of 53.6 months (range, 2.8-114.9 months), the 5-year local failure-free survival (LFFS), regional failure free survival (RFFS), distant failure-free survival (DFFS), and overall survival (OS) were 84.1%, 92.2%, 74.1%, and 63.0%, respectively. At their last follow-up visit, 118 patients (35.2%) had developed treatment failure. Distant metastasis was the major failure pattern after treatment. The most common toxicities were mainly in grade 1 or 2. Concurrent chemotherapy failed to improve survival rates for patients with T4 classification NPC. CONCLUSION: The results of T4 classification NPC treated by IMRT were excellent, and distant metastasis was the most commonly failure pattern. Treatment-related toxicities were well tolerable. The role of concurrent chemotherapy for T4 classification NPC needs to be further investigated in the era of IMRT.

Primary radiotherapy compared with primary surgery in cervical esophageal cancer.

IMPORTANCE: The management of cervical esophageal cancer (CEC) is controversial. The advantages of radiotherapy (RT) for CEC are lower rates of acute morbidity and mortality compared with surgery and potential for larynx preservation. The advantage of surgery is that the transposed stomach may function better over the long term than an irradiated esophagus, which tends to become stenotic over time. Which one is the primary treatment of CEC? OBJECTIVE: To evaluate treatment outcomes of primary RT and primary surgery in patients with CEC. DESIGN, SETTING, AND PARTICIPANTS: This retrospective study conducted in a university hospital included 224 patients treated for CEC between 2001 and 2012. INTERVENTIONS: One hundred and sixty-one patients who received primary RT with or without subsequent surgery were assigned to the RT group, including 133 patients who received RT alone or RT with concurrent chemotherapy and 28 patients who received preoperative RT plus surgery. Sixty-three patients who received primary surgery with or without subsequent RT were assigned to the primary surgery group, including 27 patients who received surgery alone and 36 patients who received surgery plus postoperative RT. MAIN OUTCOMES AND MEASURES: The rates of overall 2-year local failure-free survival (FFS), regional FFS, distant FFS, and overall survival for patients undergoing primary RT and primary surgery were compared. A separate analysis using matched cases between the primary RT group and primary surgery group was conducted. RESULTS: The median follow-up time was 15.1 months. The rates of overall 2-year local FFS, regional FFS, distant FFS, and overall survival for patients undergoing primary RT and primary surgery were 69.9% and 68.6%, 79.5% and 69.8%, 74.3% and 62.5%, 49.3% and 50.7%, respectively (P > .05 for all). Matched-case analyses did not show any significant differences in measured survival rates between the treatment groups. CONCLUSIONS AND RELEVANCE: Given the similarities in rates of local FFS, regional FFS, distant FFS, and overall survival between the primary RT and primary surgery CEC treatment groups, we recommend primary RT for larynx preservation, with surgery offered subsequently for patients who do not respond to RT.

Pattern of Failure in Surgically Treated Patients with Cervical Esophageal Squamous Cell Carcinoma.

OBJECTIVE: The aim of this study was to analyze the pattern of failure in patients who have undergone surgical resection for cervical esophageal squamous cell carcinoma. STUDY DESIGN: Case series with chart review. SETTING: University hospital. SUBJECTS AND METHODS: Sixty-two patients who had undergone surgical resection of cervical esophageal squamous cell carcinoma from January 2001 through April 2012. Sites of failure were documented. RESULTS: Twenty-nine patients had developed treatment failure. Of the 29 patients, 14, 13, and 14 had developed local failure, regional failure, and distant metastasis, respectively. Of the 13 regional failures, the images of 2 patients were lost. The other 11 regional failures included left lateral nodal disease at level II (n = 2), level III (n = 4), and level IV (n = 7); right lateral nodal disease at level II (n = 2), level III (n = 3), and level IV (n = 3); and level VI (n = 4). The overall 2-year local failure-free survival rate and regional failure-free survival rates were 79.6% and 58.6% (P = .04) for patients with stage II disease and 79.6% and 59.6% (P = .054) for patients with stage III disease, respectively. CONCLUSIONS: The pattern of failure of cervical esophageal squamous cell carcinoma is characterized by early locoregional failure, especially in patients with stage III disease.

Recurrence of nasopharyngeal carcinoma in the parotid region after definitive intensity-modulated radiotherapy.

PURPOSE: To discuss the clinical characteristics and management of periparotid recurrence of nasopharyngeal carcinoma after definitive intensity-modulated radiotherapy. PATIENTS AND METHODS: The authors retrospectively reviewed the charts of 716 patients with nasopharyngeal carcinoma who underwent intensity-modulated radiotherapy at their center from January 2005 through December 2010. Disease recurred in a spared parotid gland in 10 patients (1.4%). After periparotid recurrence, 4 patients received surgery alone, 1 patient received radiotherapy alone, 2 patients received chemotherapy alone, 2 patients received surgery plus chemotherapy, and 1 patient received surgery plus radiotherapy. RESULTS: After a median follow-up of 42.6 months (19.8 to 86.0 months), 4 patients died of tumor progression. The median survival time after periparotid recurrence was 25.1 months (5.0 to 74.5 months). CONCLUSIONS: Periparotid recurrence is an uncommon pattern of failure after definitive intensity-modulated radiotherapy for nasopharyngeal carcinoma, and there were some long-term survivors in this patient population after salvage treatment.

Clinical characteristics and patterns of failure in the parotid region after intensity-modulated radiotherapy for nasopharyngeal carcinoma.

OBJECTIVE: To discuss the clinical characteristics and patterns of failure in the parotid region after intensity-modulated radiotherapy for nasopharygeal carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the charts of 716 patients with nasopharygeal carcinoma who underwent intensity-modulated radiotherapy in our centre from January 2005 to December 2010. Disease recurred in a spared parotid gland in 10 patients (1.4%). There were 2 females and 8 males with a median age of 38.5 (34-53) years. The most common presenting symptom was a swelling in pre-auricular region (7/10). Parotid glands were spared bilaterally in these patients. None of these patients had undergone previous radiotherapy or surgical treatment of the head and neck. The location of periparotid failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. RESULTS: The median time from day 1 of radiotherapy to periparoid recurrence was 17.4 (4.4-40.5) months. The median survivial after periparoid recurrence was 25.1 (5.0-74.5) months. There were 9 (90%) patients with lateral retropharyngeal lymphadenopathy. Seven of the periparotid failures were marginal. Of the 7 marginal failures, 6 occurred at the ipslateral parotid of the primary tumor centre. The average mean dose of the ipslateral parotid was 38.1 (32.3-44.1) Gy. CONCLUSION: Periparotid recurrence is an uncommon pattern of failure after definitive intensity-modulated radiotherapy for nasopharygeal carcinoma. To reduce the risk of periparotid recurrence,one possible strategy is to lessen the dose constraint criteria to ipslateral parotid of the primary tumor centre especially for nasopharygeal carcinoma with lateral retropharyngeal lymphadenopathy.

Management of nasopharyngeal adenoid cystic carcinoma.

PURPOSE: Nasopharyngeal adenoid cystic carcinomas (NACCs) are rare. No clear consensus is available regarding clinical characteristics and management approaches. The aim of this study was to summarize the clinical characteristics and evaluate the management approaches of NACC. MATERIALS AND METHODS: The experience of 1 institution with this tumor and the outcomes of treatment were examined. The medical records of 36 patients with NACC at 1 institution from 1963 through 2006 were reviewed. RESULTS: After a median follow-up of 65.8 months (1.8 to 245.2 mo), the 5- and 10-year overall survival, locoregional failure-free survival, and distant metastasis failure-free survival rates were 70.2% and 31.6%, 63.4% and 49.1%, and 65.0% and 59.6%, respectively. No significant differences were found in locoregional failure-free survival, distant metastasis failure-free survival, or overall survival rates between the group that received radiotherapy alone and the group that received combined modality therapy (radiotherapy plus surgery or surgery plus radiotherapy). CONCLUSIONS: NACC is a malignancy with a generally favorable prognosis. Radiotherapy alone or a combined modality therapy (radiotherapy plus surgery or surgery plus radiotherapy) is effective in the treatment of NACC.

Clinical outcomes and patterns of failure after intensity-modulated radiotherapy for T4 nasopharyngeal carcinoma.

The goal of this study is to study and report the clinical outcomes and patterns of failure after intensity-modulated radiotherapy (IMRT) for T4 nasopharyngeal carcinoma (NPC). A total of 70 patients treated with IMRT between 2004 and 2009 were eligible for study inclusion. According to the staging system of 2010 AJCC, all the primary tumors were attributed to T4 stage, while the distribution of disease by N stage was N0 in 2, N1 in 23, N2 in 39, N3a in 1, and N3b in 5. The location and extent of locoregional failures were transferred to the pretreatment planning computed tomography for dosimetry analysis. The median follow-up period was 26.8 (range, 4-78) months. The overall 2-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 82.1%, 92.3%, 73.8%, and 82.5%, respectively. Thirty-three patients had developed treatment failure. Of the 33 patients, 11, 2, and 15 had developed local failure, regional failure, and distant metastasis, respectively, 2 had developed locoregional failure, 1 had developed distant metastasis and failure at the primary, and 2 had developed distant metastasis and failure at the primary and nodal site. Eight of the locoregional failures were marginal. The results of treating T4 NPC with IMRT were excellent. Advanced T4 disease remained difficult to treat. One possible strategy is to lessen the dose constraint criteria of selected neurologic structures. Distant metastasis remains the most difficult treatment challenge for patients with T4 NPC at present, and more effective systemic chemotherapy should be explored.