Salivary gland tumors treated with adjuvant intensity-modulated radiotherapy with or without concurrent chemotherapy.

PURPOSE: To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. PATIENTS AND METHODS: We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. RESULTS: The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). CONCLUSIONS: Treatment of salivary gland malignancies with postoperative IMRT was well tolerated with a high rate of local control. Chemoradiotherapy resulted in excellent local control in a subgroup of patients with adverse prognostic factors and might be warranted in select patients.

Treatment of oral cavity squamous cell carcinoma with adjuvant or definitive intensity-modulated radiation therapy.

PURPOSE: The optimal management of oral cavity squamous cell carcinoma (OCSCC) typically involves surgical resection followed by adjuvant radiotherapy or chemoradiotherapy (CRT) in the setting of adverse pathologic features. Intensity-modulated radiation therapy (IMRT) is frequently used to treat oral cavity cancers, but published IMRT outcomes specific to this disease site are sparse. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for OCSCC. METHODS AND MATERIALS: Retrospective study of all patients treated at Dana-Farber Cancer Institute for OCSCC with adjuvant or definitive IMRT between August 2004 and December 2009. The American Joint Committee on Cancer disease stage criteria distribution of this cohort included 5 patients (12%) with stage I; 10 patients (24%) with stage II (n = 10, 24%); 14 patients (33%) with stage III (n = 14, 33%); and 13 patients (31%) with stage IV. The primary endpoint was overall survival (OS); secondary endpoints were locoregional control (LRC) and acute and chronic toxicity. RESULTS: Forty-two patients with OCSCC were included, 30 of whom were initially treated with surgical resection. Twenty-three (77%) of 30 surgical patients treated with adjuvant IMRT also received concurrent chemotherapy, and 9 of 12 (75%) patients treated definitively without surgery were treated with CRT or induction chemotherapy and CRT. With a median follow-up of 2.1 years (interquartile range, 1.1-3.1 years) for all patients, the 2-year actuarial rates of OS and LRC following adjuvant IMRT were 85% and 91%, respectively, and the comparable results for definitive IMRT were 63% and 64% for OS and LRC, respectively. Only 1 patient developed symptomatic osteoradionecrosis, and among patients without evidence of disease, 35% experienced grade 2 to 3 late dysphagia, with only 1 patient who was continuously gastrostomy-dependent. CONCLUSIONS: In this single-institution series, postoperative IMRT was associated with promising LRC, OS, and lower late toxicity rates, and chemoradiotherapy was a successful treatment for patients with high-risk disease. In contrast, outcomes of radiation-based treatment for patients with inoperable locally advanced disease were markedly less successful.

Swallowing function following postchemoradiotherapy neck dissection: review of findings and analysis of contributing factors.

OBJECTIVE: This study assesses swallowing function following chemoradiotherapy and neck dissection in head and neck cancer patients and investigates clinical, treatment, and neck dissection factors associated with dysphagia. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: Eighty-eight patients undergoing neck dissection after chemoradiotherapy for advanced head and neck cancer were reviewed. Dysphagia outcome measures included weight loss, diet, gastrostomy tube (GT) dependency,and video swallow findings of aspiration or stenosis. In addition,the researchers created a Diet/GT Scale, with scores ranging from 1 to 5. Univariate and multivariate analysis of clinical, treatment, or neck dissection factors potentially associated with dysphagia outcome measures was undertaken. RESULTS: Peak mean weight loss was 17% at 6 months after chemoradiotherapy. At 12 months, a soft/regular diet was taken by 78 of 88 patients (89%), and only 1 of 88 patients (1%)was nil per os. Gastrostomy tube dependence at 6, 12, and 24 months was 53%, 25%, and 10%, respectively. The Diet/GT score was 5 (gastrostomy tube removed and soft/regular diet)for 47% at 6 months, 74% at 12 months, and 89% at 24 months.Multivariate analyses revealed that higher tumor stage was associated with a lower Diet/GT score at 12 months (P = .02)and gastrostomy dependence at 12 months (P = .01) and 24 months (P = .04). CONCLUSION: Despite the addition of neck dissection to chemoradiotherapy,nearly all patients took a soft or regular diet and reached a Diet/GT score of 5, and only 1% remained nil per os. A higher tumor stage is associated with a lower Diet/GT score and gastrostomy tube dependency beyond 12 months.

Efficacy and toxicity of chemoradiotherapy using intensity-modulated radiotherapy for unknown primary of head and neck.

PURPOSE: No single standard treatment paradigm is available for head-and-neck squamous cell carcinoma of an unknown primary (HNCUP). Bilateral neck radiotherapy with mucosal axis irradiation is widely used, with or without chemotherapy and/or surgical resection. Intensity-modulated radiotherapy (IMRT) is a highly conformal method for delivering radiation that is becoming the standard of care and might reduce the long-term treatment-related sequelae. We report the Dana-Farber Cancer Institute experience with IMRT-based treatment for HNCUP. PATIENTS AND MATERIALS: A retrospective study of all patients treated at the Dana-Farber Cancer Institute for HNCUP with IMRT between August 2004 and January 2009. The primary endpoint was overall survival; the secondary endpoints were locoregional and distant control, and acute and chronic toxicity. RESULTS: A total of 24 patients with HNCUP were included. Of these patients, 22 had Stage N2 disease or greater. All patients underwent neck computed tomography, positron emission tomography-computed tomography, and examination under anesthesia with directed biopsies. Of the 24 patients, 22 received concurrent chemotherapy, and 7 (29%) also underwent induction chemotherapy. The median involved nodal dose was 70 Gy, and the median mucosal dose was 60 Gy. With a median follow-up of 2.1 years, the 2-year actuarial overall survival and locoregional control rate was 92% and 100%, respectively. Only 25% of the patients had Grade 2 xerostomia, although 11 patients (46%) required esophageal dilation for stricture. CONCLUSION: In a single-institution series, IMRT-based chemoradiotherapy for HNCUP was associated with superb overall survival and locoregional control. The xerostomia rates were promising, but the aggressive therapy was associated with significant rates of esophageal stenosis.

Utilizing computed tomography as a road map for designing selective and superselective neck dissection after chemoradiotherapy.

OBJECTIVE: To determine whether computed tomography can distinguish low risk neck levels that can be omitted when neck dissection is undertaken after chemoradiotherapy. STUDY DESIGN: Case series with chart review. SETTING: Tertiary care center. SUBJECTS AND METHODS: Head and neck squamous cell carcinoma patients undergoing neck dissection after chemoradiotherapy between January 1998 and June 2008. We compared computed tomography findings after chemoradiotherapy with neck dissection pathology results; used primary location and computed tomography findings to design selective or superselective neck dissection; and determined whether these surgeries would have contained all metastatic disease. RESULTS: A total of 104 patients were identified, providing 110 heminecks, 531 neck levels, and 3009 lymph nodes for analysis. Neck dissections were positive in 20 (19%) of 104 patients, corresponding to 20 hemineck dissections, 31 neck levels, and 53 lymph nodes. The negative predictive value for computed tomography was 95 percent. The negative predictive value for computed tomography per neck level was as follows: I, 100 percent; II, 96 percent; III, 96 percent; IV, 97 percent; and V, 96 percent. A selective neck dissection or a superselective neck dissection, guided by level specific computed tomography findings and limited to necks with post treatment partial response in one level, would have captured all disease in 52 (95%) of 55 and 51 (93%) of 55 heminecks. CONCLUSION: Negative computed tomography accurately predicts pathologic complete response at neck dissection. Neck dissection can be avoided in these patients. Additionally, computed tomography reliably identifies low risk neck levels that do not require dissection, permitting selective neck dissection or superselective neck dissection in partial response patients with limited residual disease.

Efficacy and toxicity of reirradiation using intensity-modulated radiotherapy for recurrent or second primary head and neck cancer.

BACKGROUND: Patients with locally recurrent squamous cell cancer of the head and neck (SCCHN) are reported to have a poor prognosis and limited therapeutic options. Optimal management is selectively applied and morbid. Both surgical resection and chemoradiotherapy are reported to result in median survivals of approximately 12 months. Intensity-modulated radiotherapy (IMRT) is a highly conformal approach for delivering RT. This study reported the experience of the Dana-Farber Cancer Institute (DFCI) with IMRT-based chemoradiotherapy with or without surgery for locally recurrent SCCHN. METHODS: The current study was a retrospective study of all patients treated at DFCI who were diagnosed with nonmetastatic second primary or recurrent SCCHN and who received reirradiation based on IMRT. The primary endpoint was overall survival (OS), and secondary endpoints were locoregional (LRC) and distant control and acute and chronic toxicity. RESULTS: Thirty-five patients were treated from August 2004 until December 2008. Recurrent disease was treated in the oral cavity (4 patients), larynx/hypopharynx (13 patients), oropharynx (7 patients), nasopharynx (2 patients), and neck (9 patients). The median radiation dose was 60 Gray (Gy), and all patients received concurrent chemotherapy. The median follow-up was 2.3 years. The 2-year actuarial OS and LRC rates were 48% and 67%, respectively. Approximately 91% and 46%, respectively, of all patients developed at least 1 acute and late grade 3 toxicity. Four (11%) late deaths occurred in patients with no evidence of disease (2 aspiration events, 1 oropharyngeal hemorrhage, and 1 infectious death). CONCLUSIONS: Aggressive chemoradiotherapy with IMRT was found to be feasible and resulted in favorable survival outcomes in comparison with published reports. Acute and late toxicities were substantial. The apparently improved LRC appears to carry a significant risk of developing late complications.

Combined antegrade and retrograde esophageal dilation for head and neck cancer-related complete esophageal stenosis.

OBJECTIVES/HYPOTHESIS: Assess the safety and efficacy of combined antegrade and retrograde esophageal dilation (CARD) for complete esophageal stenosis following head and neck cancer (HNC) treatment. Review HNC dysphagia management. STUDY DESIGN: Retrospective review of all patients undergoing CARD following HNC treatment between May 2001 and September 2008. METHODS: Forty-five patients were identified for review. Parameters assessed included: ability to obtain intraoperative esophageal patency, complications, number of dilations required, diet, and gastric tube (GT) status. Factors associated with dilation failure were analyzed. RESULTS: Intraoperative esophageal patency was obtained in 91% of patients. Median number of all dilations per patient was three. Median number of CARDs per patient was one. Resumption of oral intake occurred in 36/45 (80%). Diet results included: regular or soft diet 32/45 (71%), GT removal 27/45 (60%), and GT dependence with nothing by mouth 9/45 (20%). Laryngeal and pharyngeal stenosis, radionecrosis, tracheotomy dependence, and elongated stenosis were associated with dilation failure. Complications occurred in 18/63 (29%) CARD procedures: eight pneumomediastinum, seven GT site problems, two esophageal perforations, and one pharyngeal infection. All complications resolved spontaneously or with minimal interventions. CONCLUSIONS: CARD was safe and effective. Intraoperative patency was achieved in 91% of patients. Eighty percent resumed oral intake. The majority of patients had their GTs removed and resumed a soft or regular diet. Dilation failure was associated with laryngeal, pharyngeal, and excessively long esophageal stenosis, often resulting from radionecrosis. Complications were minor. CARD should be considered before relegating patients with complete esophageal stenosis to chronic GT dependence or subjecting them to laryngopharyngo esophagectomy.

A fluoroscopic and laryngoscopic study of glossopharyngeal insufflation and exsufflation.

Glossopharyngeal breathing, frequently performed by elite breath-hold divers, relies on muscles of the mouth and pharynx to move air into (glossopharyngeal insufflation, GI) and out of the lungs (glossopharyngeal exsufflation, GE). GI has also been used by patients with weak respiratory muscles. Fluoroscopic and endoscopic examinations were performed on four divers (three of whom were world record holders) during both GI and GE maneuvers. A detailed pictorial description of both GI and GE, with online video material that includes external, endoscopic and fluoroscopic examinations, is provided in this publication. Both GI and GE are accomplished with a coordinated series of contractions by glossopharyngeal muscles and they rely on a piston pump-like action of the larynx. In particular, the larynx moves extensively and repeatedly up and down, to either inject air into (GI) or extract it from the lungs (GE), with the vocal cords functioning as a valve. During both maneuvers, when the larynx is in its highest position, the epiglottis does not fold back, unlike what happens during swallowing.

A pilot surrogate endpoint biomarker study of celecoxib in oral premalignant lesions.

This study evaluated changes in prostaglandin E(2) (PGE(2)) levels and related biomarkers in oral premalignant lesions (OPL) in response to celecoxib treatment. Twenty-two subjects were enrolled and treated with celecoxib. Pretreatment and 12-week biopsies were done. Subjects whose biopsy showed >or=30% decrease in PGE(2) remained on celecoxib for a total of 12 months when repeat biopsy was done. Biopsies were examined to assess degree of dysplasia, DNA ploidy, and immunohistochemical expression of BCL2, pAKT-Ser473, Ki-67, and CD31 (microvessel density). In 18 paired biopsies available at baseline and 12 weeks, mean normalized PGE(2) levels decreased by 38% (P = 0.002). After 12 months, PGE(2) decreased by 31% (P = 0.340). Twelve biopsies (67%; P = 0.0129) showed improvement in degree of dysplasia after 12 weeks, and 8 of 11 biopsies (73%; P = 0.0703) continued to show an improvement in the degree of dysplasia after 12 months. Trends suggested down-modulation of cyclooxygenase-2 and Ki-67 in some tissues, increased pAKT-Ser473 expression, and an inverse relationship between PGE(2) and BCL2 expression. This study documents the feasibility of measuring potential surrogate endpoint biomarkers of chemopreventive agent response in OPLs. Treatment with celecoxib in subjects with OPLs favorably modulates the primary mediator of cyclooxygenase-2 activity, PGE(2), after 12 weeks.

Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer.

BACKGROUND: A randomized phase 3 trial of the treatment of squamous-cell carcinoma of the head and neck compared induction chemotherapy with docetaxel plus cisplatin and fluorouracil (TPF) with cisplatin and fluorouracil (PF), followed by chemoradiotherapy. METHODS: We randomly assigned 501 patients (all of whom had stage III or IV disease with no distant metastases and tumors considered to be unresectable or were candidates for organ preservation) to receive either TPF or PF induction chemotherapy, followed by chemoradiotherapy with weekly carboplatin therapy and radiotherapy for 5 days per week. The primary end point was overall survival. RESULTS: With a minimum of 2 years of follow-up (> or =3 years for 69% of patients), significantly more patients survived in the TPF group than in the PF group (hazard ratio for death, 0.70; P=0.006). Estimates of overall survival at 3 years were 62% in the TPF group and 48% in the PF group; the median overall survival was 71 months and 30 months, respectively (P=0.006). There was better locoregional control in the TPF group than in the PF group (P=0.04), but the incidence of distant metastases in the two groups did not differ significantly (P=0.14). Rates of neutropenia and febrile neutropenia were higher in the TPF group; chemotherapy was more frequently delayed because of hematologic adverse events in the PF group. CONCLUSIONS: Patients with squamous-cell carcinoma of the head and neck who received docetaxel plus cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy had a significantly longer survival than did patients who received cisplatin and fluorouracil induction chemotherapy plus chemoradiotherapy. (ClinicalTrials.gov number, NCT00273546 [ClinicalTrials.gov].).

Rate of pathologic complete responses to docetaxel, cisplatin, and fluorouracil induction chemotherapy in patients with squamous cell carcinoma of the head and neck.

OBJECTIVE: To report the rate of pathological complete response after induction chemotherapy with the docetaxel, cisplatin, and fluorouracil (TPF) combination. DESIGN: Retrospective cohort analysis. SETTING: Tertiary care academic cancer center, between June 1999 and May 2004. PATIENTS: Seventy-two patients with newly diagnosed squamous cell carcinoma of the head and neck; 68 (95%) of the patients had stage IV, locally advanced disease. INTERVENTIONS: Three cycles of induction chemotherapy followed by a biopsy of the primary site. All patients subsequently underwent chemotherapy with 3 cycles of TPF. MAIN OUTCOME MEASURE: Rate of pathological complete response at the primary site after induction chemotherapy with 3 cycles of TPF. RESULTS: Biopsy results were negative for cancer in 64 patients (89%) and positive in 8 patients (11%). The median follow-up was 2 years. In the positive biopsy result group, 2 (25%) of 8 patients died of disease vs 3 (4%) of 64 patients in the negative biopsy result group. Twenty-nine neck dissections were performed; results were positive in 7 patients (all alive with no evidence of disease) and negative in 22 patients (21 alive with no evidence of disease). The overall 2- and 5-year progression-free survival is currently projected at 85% and 85%, respectively; the overall 2- and 5-year survival, at 95% and 90%, respectively. Importantly, T4 presentation did not predict a positive biopsy result at the primary site or a positive neck dissection result (P = .60 and P = .56, respectively). N3 presentation (12 patients) did not predict a positive biopsy result at the primary site (P = .87) but did correlate with positive neck dissection results in 6 of 12 patients (P<.001). CONCLUSIONS: Induction chemotherapy with the TPF regimen results in a high pathological complete response rate (89%). This rate is higher than with the cisplatin plus fluorouracil combination therapy, which was reported to be between 25% and 50% in previous studies. Chemoradiotherapy is currently an accepted standard of care, but induction chemotherapy continues to be investigated. Based on recent phase 3 trial results and the data presented herein, we propose that the 3-drug combination be used as the new platform when administering induction chemotherapy.

Concurrent weekly docetaxel and concomitant boost radiation therapy in the treatment of locally advanced squamous cell cancer of the head and neck.

PURPOSE: In a Phase I/II trial, we investigated concurrent weekly docetaxel and concomitant boost radiation in patients with locally advanced squamous cell cancer of the head and neck (SCCHN) after induction chemotherapy. PATIENTS AND METHODS: Patients presented with American Joint Committee on Cancer Stage III/IV and were treated initially with induction chemotherapy using cisplatinum/5-fluorouracil (PF), carboplatinum-5-FU, or docetaxel-PF. Patients then received docetaxel four times weekly with concomitant boost (CB) radiation (1.8 Gy once-daily X20, 1.8/1.5 Gy twice a day). Fifteen patients each received 20 mg/M2 and 25 mg/M2. RESULTS: Thirty-one patients were enrolled and 30 were evaluable for response and toxicity. Median follow-up was 42 months (range, 27-63 months). Primary sites were: oropharynx 19, oral cavity 2, larynx/hypopharynx 5, and unknown primary 4. Eighty-seven percent of patients had N2/N3 disease; 60% had T3/T4 disease. Twenty percent of patients had a complete response (CR) to induction chemotherapy. After chemoradiotherapy, 21 of 30 patients had a CR, 2 had progressive disease, and 7 had partial response (PR). Nineteen of 26 patients presenting with neck disease had neck dissections, and 7 of 19 were positive. Ninety-three percent of all patients were rendered disease-free after all planned therapy. Treatment failed in 8 patients, and 7 have died of disease. An additional patient died with no evidence of disease. Twenty-one patients (70%) are currently alive with no evidence of disease. No acute dose-limiting toxicity was observed at either dose level. CONCLUSIONS: This intensive treatment regimen of concurrent docetaxel/concomitant boost radiation and surgery after induction chemotherapy in poor prognosis patients yields good local regional control and survival. Docetaxel/CB chemoradiotherapy represents an aggressive alternative regimen to platinum-based chemoradiotherapy or surgery in patients who have a poor response to induction chemotherapy.

Examining the need for neck dissection in the era of chemoradiation therapy for advanced head and neck cancer.

OBJECTIVES: To (1) determine clinical factors that predict pathologic complete response (pCR) on neck dissection after sequential chemoradiotherapy (SCRT) for advanced head and neck cancer and (2) compare survival parameters between those who underwent neck dissection and those who did not among those patients with a clinical complete response (cCR) in the neck after SCRT, thus assessing the benefit of neck dissection in patients with a cCR in the neck. DESIGN: Retrospective review with a mean follow-up of 3.5 years. SETTING: Regional cancer center. PATIENTS: The study population comprised 55 patients undergoing SCRT for advanced head and neck cancer with N2 or N3 neck disease. Three patients developed progressive disease and were excluded, and 28 patients underwent neck dissection. INTERVENTIONS: Patients were assessed by physical examination and radiographically after SCRT. MAIN OUTCOME MEASURES: Physical examination and radiographic assessments of residual neck disease were compared with pathologic findings in those patients who underwent neck dissection. Survival comparisons were made between patients with a cCR in the neck who underwent neck dissection and those who did not. RESULTS: Of 28 patients who underwent neck dissection, 8 had persistent pathologically positive nodal disease: 5 (45%) of 11 had N3 and 3 (18%) of 17 had N2 disease. Individual clinical neck assessments after SCRT were fairly predictive of a negative pathologic finding at neck dissection. The negative predictive values were physical examination (75%), computed tomography or magnetic resonance imaging (71%), and positron emission tomography (75%). However, when physical examination, imaging studies, and positron emission tomography all indicated a complete response, this accurately predicted a pCR on neck dissection. There appeared to be no improvement in survival parameters when a neck dissection was performed on patients with a cCR in the neck. CONCLUSIONS: Patients with N3 disease are at high risk for residual neck metastasis after SCRT. Patients with N2 disease can be assessed with physical examination, imaging studies, and positron emission tomography. If these all indicate a cCR, then neck dissection is likely not needed. Neck dissection did not appear to further improve survival parameters for patients with a cCR in the neck.

Dysphagia after sequential chemoradiation therapy for advanced head and neck cancer.

OBJECTIVES: Assess impact of sequential chemoradiation therapy (SCRT) for advanced head and neck cancer (HNCA) on swallowing, nutrition, and quality of life. STUDY DESIGN: Prospective cohort study of 59 patients undergoing SCRT for advanced head and neck cancer. Follow-up median was 47.5 months. SETTING: Regional Cancer Center. RESULTS: Median time to gastrostomy tube removal was 21 weeks. Eighteen of 23 patients who underwent modified barium swallow demonstrated aspiration; none developed pneumonia. Six of 7 with pharyngoesophageal stricture underwent successful dilatation. Functional Assessment of Cancer Therapy-Head and Neck Scale questionnaires at median 6 months after treatment revealed "somewhat" satisfaction with swallowing. At the time of analysis, 97% have the gastronomy tube removed and take soft/regular diet. CONCLUSION: Early after treatment dysphagia adversely affected weight, modified barium swallow results, and quality of life. Diligent swallow therapy, and dilation as needed, allowed nearly all patients to have their gastronomy tubes removed and return to a soft/regular diet. SIGNIFICANCE: Dysphagia is significant after SCRT but generally slowly recovers 6 to 12 months after SCRT. EBM RATING: C-4.

Chemoradiotherapy for adenoid cystic carcinoma: preliminary results of an organ sparing approach.

OBJECTIVES: A retrospective review of primary chemoradiotherapy (CRT) for adenoid cystic carcinoma (ACC) was performed to determine if CRT might be considered as an alternative to radiotherapy and/or definitive surgery. METHODS: All treatment-naive patients with ACC of the head and neck who were treated with definitive primary chemoradiotherapy using carboplatinum and paclitaxel at Dana-Farber Cancer Institute in 2000 through 2004 were identified. Information on site, stage, presenting symptoms, performance status, treatment, toxicity, and follow up were collected and tabulated for review. RESULTS: Five patients were identified with previously untreated ACC of the head and neck who received primary carboplatinum/paclitaxel CRT for unresectability or organ preservation. Patients had a median age of 41, 4 had primaries in the paranasal sinuses invading the base of skull and 1 had a transglottic laryngeal lesion. All patients completed a course of definitive chemoradiotherapy without treatment break. Grade 3 mucosal reactions developed during CRT in all patients. With a median follow-up of 36 months (range, 20-43) all patients have local regional control; 1 patient developed distant metastases at 7 months and is alive at 20 months. CONCLUSIONS: Preliminary data suggest that carboplatinum/paclitaxel based CRT for ACC provides local regional control and is a potential alternative to surgery or radiotherapy for patients with locally advanced ACC. Carboplatinum/paclitaxel based CRT warrants further study.

Phase I study of gefitinib plus celecoxib in recurrent or metastatic squamous cell carcinoma of the head and neck.

PURPOSE: Effective and tolerable palliative treatments are needed for patients with incurable squamous cell carcinoma of the head and neck (SCCHN). Single-agent targeted therapies have limited activity in this setting. The feasibility of adding celecoxib to gefitinib for the treatment of incurable SCCHN is unknown. PATIENTS AND METHODS: Nineteen patients with unresectable recurrent locoregional and/or distant metastatic SCCHN with progressive disease after at least one prior chemotherapy or chemoradiotherapy regimen were enrolled onto this single-institution phase I study. Three dose levels were explored: (1) celecoxib 200 mg twice daily plus gefitinib 250 mg daily; (2) celecoxib 400 mg twice daily plus gefitinib 250 mg daily; and (3) celecoxib 400 mg twice daily plus gefitinib 500 mg daily. RESULTS: No dose-limiting toxicities were encountered at any dose level. The most common toxicities were acneiform rash, diarrhea, hand reaction, dyspepsia, and anemia. Four of 18 patients assessable for response (22%; 95% CI, 2% to 42%) achieved a confirmed partial response. CONCLUSION: The combination of gefitinib 500 mg daily plus celecoxib 400 mg twice daily is well-tolerated. The encouraging responses seen in this early study suggest further evaluation of epidermal growth factor receptor and cyclooxygenase-2 inhibitors in SCCHN is warranted.

Organ preservation and treatment toxicity with induction chemotherapy followed by radiation therapy or chemoradiation for advanced laryngeal cancer.

OBJECTIVES: The authors reviewed records of patients with advanced laryngeal cancer treated with induction chemotherapy (IC) and hyperfractionated radiation therapy (RT) or chemoradiation (CRT) to determine the rates of organ preservation and function. METHODS: A total of 29 patients with stage III (45%) and stage IV (55%) squamous cell carcinoma of the larynx (SCCL), were treated with IC and RT or CRT in 1 of 7 consecutive trials. Fifty-five percent had clinically node-positive disease. Fifty-five percent and 45% had T3 or T4 tumors, respectively. All received 3 cycles of platinum-based IC. Daily RT was given to 48%, twice-daily RT to 45%, and concomitant boost RT to 7%. CRT was carboplatin (28%) or docetaxel (28%). Those treated with twice-daily RT did not receive CRT. RESULTS: The median follow-up is 52 months. Overall survival is 66%. Relapse occurred in 12 patients (41%), and 6 underwent salvage laryngectomy (5 stage III, 1 stage IV). Fifty-nine percent of patients (17 of 29) are alive at last follow-up with an anatomically intact larynx, and 48% (14 of 29) are alive with a functional larynx. Of the 23 patients for whom detailed information on gastrostomy tube (g-tube) placement/removal was available, median time with g-tube was 12 months, and 15 of 23 patients (65%) had a g-tube for 6 months or more. Twenty-three of all 29 patients (79%) retained an anatomically intact larynx, but 7 of 23 (30%) never resumed their pretreatment organ function. The overall rate of functional organ preservation, regardless of survival, was 55% (16/29). The 7 of 29 patients (26%) who retained a nonfunctional larynx required permanent g-tube or were unable to return to pretreatment oral intake capability. Nine of 13 with T4 SCCL (69%) compared with 7 of 16 (44%) T3 SCCL retained a functional larynx. CONCLUSION: The rate of larynx preservation is high, but toxicity remains significant with IC followed by hyperfractionated RT or CRT in advanced laryngeal cancer. Half of all patients were alive, able to retain their larynx, and return to pretreatment function. Advanced stage was not an indicator of poor outcome.

Definitive radiotherapy with interstitial implant boost for squamous cell carcinoma of the tongue base.

BACKGROUND: The purpose of this study was to examine the long-term outcome of a cohort of patients with unresected base of tongue carcinoma who received interstitial brachytherapy after comprehensive external beam radiation therapy. METHODS: Between 1983 and 2000, 122 patients with primary or recurrent squamous cell carcinoma of the oropharynx or oral cavity received interstitial brachytherapy as part of their overall management. Forty patients had primary, unresected carcinoma of the base of tongue and are the subjects of this analysis. The median age was 54 years. Fifty-four percent had T3 or T4 disease, and 70% had clinical or radiographic lymphadenopathy. Twenty-four (60%) received two to three cycles of neoadjuvant chemotherapy. The oropharynx, bilateral neck, and supraclavicular fossae were comprehensively irradiated, and the tongue base received a median external beam dose of 61.2 Gy (50-72 Gy). The primary site was then boosted with an interstitial 192Iridium implant by use of a gold-button single-strand technique and three-dimensional treatment planning. The dose rate was prescribed at 0.4 to 0.5 Gy/hr. The median implant dose was 17.4 Gy (9.6-24 Gy) and adjusted to reach a total dose to the primary tumor of 80 Gy. N2 to 3 disease was managed by a planned neck dissection performed at the time of the implant. RESULTS: The median follow-up for all patients was 56 months, and the overall survival rates were 62% at 5 years and 27% at 10 years. The actuarial primary site control was 78% at 5 years and 70% at 10 years. The overall survival and primary site control were independent of T classification, N status, or overall stage. Systemic therapy was associated with an improvement in overall survival (p = .04) and a trend toward increased primary site control with greater clinical response. There were seven documented late effects, the most frequent being grade 3 osteonecrosis (n = 2), grade 2 swallowing dysfunction (n = 2), trismus (n = 2), and chronic throat pain (n = 1). CONCLUSIONS: In an era of greatly improved dose distributions made possible by three-dimensional treatment planning and intensity-modulated radiation therapy, brachytherapy allows a highly conformal dose to be delivered in sites such as the oropharynx. If done properly, the procedure is safe and delivers a dose that is higher than what can be achieved by external beam radiation alone with the expected biologic advantages. The long-term data presented here support an approach of treating advanced tongue base lesions that includes interstitial brachytherapy as part of the overall management plan. This approach has led to a 78% rate of organ preservation at 5 years, with a 5% incidence of significant late morbidity (osteonecrosis) that has required medical management.

Induction chemotherapy in locally advanced squamous cell cancer of the head and neck: evolution of the sequential treatment approach.

Cisplatin plus 5-fluorouracil (5-FU) (PF regimen) induction chemotherapy (IC) has been studied over the last two decades and has proven to be a durable and effective therapy for patients with locally advanced squamous cell cancer of the head and neck (SCCHN). Although randomized trials and meta-analyses have demonstrated that PF-based IC improves survival, reduces systemic metastases, and permits organ preservation, the effect on overall survival has been less robust than the results seen with cisplatin-based chemoradiotherapy (CRT) regimens. Differences in trial design, scheduling, and surgical interventions account for some of the variation in results. As studies have evolved, it has become evident that there are advantages to both approaches. This perception has led to the concept of sequential therapy (ST), the combination of IC, CRT, and surgery. ST programs are being studied intently in many centers. Phase II and III trials of ST regimens have reported unprecedented survival results in patients with locally advanced disease. In addition, the hypothesis that PF plus a taxane may result in an improved survival, compared to PF alone, for patients with locally advanced SCCHN on ST treatments is being tested in phase III trials. Although ST has not been compared head to head with CRT, early results support the use of this treatment paradigm in patients with poor prognosis SCCHN and should lead to definitive phase III trials in the near future. ST may represent the cutting edge of therapy for patients with curable, locally advanced SCCHN.

Endoscopic management of hypopharyngeal stenosis after organ sparing therapy for head and neck cancer.

OBJECTIVES: The objective of this study was to describe and evaluate the efficacy of an endoscopic technique for the management of postchemoradiation hypopharyngeal stenosis in head and neck cancer patients. STUDY DESIGN: Retrospective review. METHODS: Patients with postchemoradiation hypopharyngeal stenoses were identified from the Dana Farber Cancer Institute head and neck database. Patients who had undergone extirpative surgery and reconstruction were excluded. All patients underwent either anterograde dilatation (AD) by the lead author (C.A.S.) or transgastric retrograde esophagoscopy with anterograde dilatation (TREAD) (C.A.S., M.T.J.). Chemoradiation records, clinic notes, operative reports, and swallowing test data were reviewed. Removal of the gastric feeding tube was considered the endpoint of rehabilitation. RESULTS: Seventeen patients had postcricoid stenoses identified by modified barium swallow. Endoscopy confirmed 15 postcricoid stenoses and 2 proximal esophageal stenoses. Nine (53%) patients had partial stenoses, and eight (47%) had complete stenoses. Eight partial stenosis patients underwent 10 AD procedures and 3 TREAD procedures. Eight complete stenosis patients underwent 9 TREAD procedures and 26 subsequent AD procedures. Fifteen of 16 (93%) patients resumed swallowing after dilatation. Thirteen (81%) patients maintained their weight on an oral diet and had their gastric feeding tubes removed. Complications included hypopharyngeal perforation (13%), abdominal wall infection (6%), stomach wall dehiscence (6%), and chondroradionecrosis of the cricoid cartilage (6%). CONCLUSIONS: Postcricoid hypopharyngeal stenosis may be partial or complete after organ sparing chemoradiation for head and neck cancer. Using the TREAD technique, successful rehabilitation of swallowing can be achieved with a low incidence of complications.