Current management of xerostomia in head and neck cancer patients.

Radiotherapy (RT) continues to play a key role in the management of head and neck cancer (HNC). Xerostomia remains a principal detriment to the quality of life (QoL) for 80 % of surviving patients receiving head and neck radiation. Radiation-induced injury to the salivary glands is dose-dependent, and thus efforts have been focused on decreasing radiation to the salivary glands. Decreased saliva production reduces both short-term and long-term quality of life in head and neck survivors by impacting on taste and contributing to dysphagia. Several radioprotective agents to the salivary gland have been investigated. Although not widely practiced, surgical transfer of the submandibular gland prior to RT is the mainstay of surgical options in preventing xerostomia. This review focuses on the strategies to improve xerostomia following radiation therapy in head and neck cancers.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multicenter international pooled validation study.

PURPOSE: There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions. PATIENTS AND METHODS: We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions. RESULTS: In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I (2) statistic = 0). CONCLUSION: Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research.

BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research.

BACKGROUND: We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN-). METHODS: A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990-2011) had pN- disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan-Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis. RESULTS: A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN-. The 5-year OS and DSS of cN- patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates. CONCLUSIONS: Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN- nodes.

Bone or cartilage invasion by advanced head and neck cancer: intra-arterial supradose cisplatin chemotherapy and concomitant radiotherapy for organ preservation.

BACKGROUND: Invasion of bony or cartilaginous structures by advanced upper aerodigestive tract cancer has been considered an indication for surgery on the basis of historic experience of poor responsiveness to radiation therapy. At University of Tennessee-Memphis, patients with advanced head and neck cancer have been treated on a protocol of concomitant intra-arterial (targeted) cisplatin and conventional radiation therapy. OBJECTIVE: To compare the efficacy, in terms of disease control and survival, of this protocol in patients with T4 squamous cell cancers and invasion of bony or cartilaginous structures (group 1; n = 45) vs those with T4 disease but no bone or cartilage involvement (group 2; n = 90). DESIGN: Subset analysis of protocol database and retrospective chart review. METHODS: Treatment consisted of 4 weekly intra-arterial infusions of cisplatin (150 mg/m(2) per week), with simultaneous systemic neutralization by intravenous sodium thiosulfate (9 mg/m(2)), and concurrent radiation therapy at 180 rad (1.8 Gy) or 200 rad (2 Gy) per fraction to a planned total of 6600 to 7400 rad (66-74 Gy) to the primary site or overt nodal disease. Presence of bone or cartilage invasion was established by review of tumor diagrams of clinical findings and computed tomography or magnetic resonance imaging reports. RESULTS: Of 135 patients who had T4 disease and a minimum follow-up of 9 months (median, 40 months), 45 had clinical or radiologic evidence of bone (n = 29: mandible, 12; maxilla, 9; sphenoid, 3; hyoid, 6) and/or cartilage (n = 18: thyroid, 16; cricoid, 4) invasion (some patients had involvement of more than 1 site). The rate of complete response in group 1 (66.7%) was not significantly different from that in group 2 (71.1%) (chi(2) test, P = .79). The 2-year overall actuarial survival for group 1 (46.3%; 95% confidence interval, 30.3%-62.3%) was not significantly different (generalized Wilcoxon test, P = .36) from that of group 2 (36.9%; 95% confidence interval, 25.5%-48.4%). A marked trend was noted for higher response rates in cases of cartilage invasion (81.2%) than in those with bone invasion (58.6%) (P = .15). CONCLUSION: Equivalent efficacy of treatment in the 2 groups suggests that targeted chemoradiation can be a definitive therapeutic option in patients with advanced head and neck cancer invading bony or cartilaginous structures.

Analysis of risk factors predictive of distant failure after targeted chemoradiation for advanced head and neck cancer.

BACKGROUND: Distant metastasis (DM) is the most common mode of recurrence among patients with advanced head and neck carcinoma treated with intra-arterial cisplatin and radiotherapy (RADPLAT). OBJECTIVE: To identify which patients are at greatest risk for DM and would benefit the most from new strategies designed to treat occult metastases. METHODS: Between 1993 and 1999, 250 patients with advanced head and neck cancer were treated by RADPLAT. Excluded from the analysis were 10 patients who either did not complete the protocol or were unavailable for follow-up and 39 patients with persistent disease or local recurrence. The incidence and the risk factors for DM in these patients were evaluated in a model that included the following factors: age, T and N classification, site of tumor, histologic grade, number (0, 1, or >1) and position (high vs low) of neck levels involved, and bilateral nodal disease. Multiple stepwise logistic regression was used for the analysis. RESULTS: In a univariate analysis, the following variables correlated to DM: N classification (P =.02), site of tumor (P =.01), lower neck nodes (P =.002), number of neck levels involved (P =.001), and bilateral nodal disease (P =.02). In a multivariate analysis, the most significant risk factors for DM were the number of neck levels involved and the site of the primary tumor (P<.001). The highest odds ratios for DM were among patients with multiple levels of nodal involvement (3.17) and patients with hypopharyngeal carcinoma (2.8). CONCLUSIONS: Patients with more than 1 level of clinical nodal involvement and patients with hypopharyngeal carcinoma have the highest risk of developing DM as the initial site of failure and would benefit most from treatment strategies that address occult distant disease.

Cancer induction in the DMBA hamster cheek pouch: a modified technique using a promoter.

OBJECTIVE: To evaluate a modified method of carcinogenesis induction using the 9,10-dimethyl-1,2-benzanthracene (DMBA) sustained-release suture technique followed by arecaidine promotion in the hamster cheek pouch model. STUDY DESIGN: Prospective, controlled animal study. METHODS: Number 3-0 cotton sutures were impregnated with DMBA and coated with silicone elastomer. These sutures were placed in the cheek pouch of Syrian hamsters in the submucosal space to a length of approximately 1.5 cm. The suture placement was confirmed every 2 weeks and replaced if lost. After 12 weeks, the DMBA-coated sutures were removed. The cheek pouches were everted and painted with a solution of arecaidine three times weekly for up to an additional 4 weeks or until the tumor reached a size of 100 mm2. RESULTS: We placed sutures in 165 Syrian hamster cheek pouches. Of these, 133 hamsters (80.6%) produced squamous cell carcinomas that reached a size of 100 mm2 and then were randomly selected for treatment in a new drug trial. Twenty-six hamsters (15.8%) were found dead and 6 (3.6%) were killed because of severe inflammation. CONCLUSIONS: The DMBA hamster cheek pouch model is a reliable and efficient animal model for inducing squamous cell carcinoma and can be used to study upper aerodigestive tract tumors.

Treatment of advanced head and neck cancer with intra-arterial cisplatin and concurrent radiation therapy: the 'RADPLAT' protocol.

The prognosis for patients presenting with advanced head and neck squamous cell carcinoma using "standard" treatment approaches, such as surgery followed by radiotherapy or radiotherapy alone, remains poor. Additionally, patients often lose their voice or swallowing ability when a primary surgical approach is used. Although systemic chemotherapy, when combined concurrently with radiotherapy, appears to be superior to radiation alone, the use of neoadjuvant or adjuvant systemic chemotherapy has not improved survival when combined with either surgery or radiotherapy. Even with the use of concurrent systemic chemotherapy and radiotherapy, the majority of the patients still succumb to their disease, usually failing locoregionally. Among the newer strategies being explored is the use of supradose intra-arterial chemotherapy (ie, cisplatin) with current radiotherapy. Acronymed "RADPLAT," this novel therapeutic approach delivers supradoses of weekly cisplatin chemotherapy with concurrent radiotherapy with acceptable toxicity, high locoregional tumor control rates, and very promising survival results. In addition, the RADPLAT approach allows for the preservation of organ function. This article reviews the evolution of the RADPLAT concept from a phase I trial to a recently completed Radiation Therapy Oncology Group trial confirming its feasibility in a multi-institutional setting.

Rationale for intralesional valrubicin in chemoradiation of squamous cell carcinoma of the head and neck.

OBJECTIVES/HYPOTHESIS: With some advanced squamous cell carcinomas (SCCs) of the head and neck, chemoradiation therapy may obviate the need for surgical intervention. However, both modalities are known to produce organ toxicities, and tumor insensitivity remains problematic. Thus there is a clear need for the development of new treatment strategies. Accordingly, preclinical studies to evaluate the use of valrubicin, a contact-safe, mechanistically novel antitumor agent, combined with low-dose radiation for the therapy of SCC have been conducted. METHODS: The comparative in vitro antitumor activities of valrubicin with or without irradiation versus cisplatin were evaluated using human-derived sensitive and cisplatin-resistant SCC cell lines. A hamster cheek pouch model of SCC was used to assess the efficacy of weekly intratumoral valrubicin injections with and without concurrent low-dose irradiation. RESULTS: Valrubicin cytotoxicity was found to be comparable in both sensitive and platinum-resistant cell lines and superior to cisplatin. The addition of minimally cytotoxic cell irradiation (300-450 cGy) resulted in prolonged G2/M cell cycle arrest and a supraadditive increase in apoptotic cell death. In hamsters, once a week x 3 intratumoral drug injections (3, 6, or 9 mg) were growth inhibitory; however, when valrubicin (6 mg) was combined with minimally cytotoxic irradiation (150, 250, or 350 cGy) significant tumor shrinkage was observed. CONCLUSIONS: Valrubicin produces supra-additive effects against SCC when combined with low-dose irradiation. This effect appears to correlate with the ability of valrubicin, a cytoplasmic-localizing drug, to inhibit protein kinase C. Therapeutic use of valrubicin against SCC could provide for reduced radiation doses with consequent improved efficacy and reduction in host toxicity.

Indications for selective neck dissection: when, how, and why.

Selective neck dissection is a procedure that is primarily indicated in patients with clinically negative nodal disease in which there is a high risk of occult metastases. Others have advocated its use for patients with positive nodes, although under very specific circumstances and in combination with postoperative radiation therapy. The type of selective neck dissection performed varies according to the site of the primary, because the pattern of metastases is unique in each case. This review presents the author's philosophy on when, how, and why to employ the procedure, based on the location of primary cancers at oral, pharyngeal, laryngeal, cutaneous, thyroid, and salivary gland sites.

Efficacy of concomitant chemoradiation and surgical salvage for N3 nodal disease associated with upper aerodigestive tract carcinoma.

OBJECTIVES/HYPOTHESIS: To determine whether an aggressive approach using trimodality therapy would improve the outcome in head and neck cancer patients with advanced (N3) nodal disease. STUDY DESIGN: In this retrospective, nonrandomized review, we analyzed a subset of patients who were treated in a targeted chemoradiation therapy protocol, consisting of 31 patients who received treatment between June 1993 and June 1997. METHODS: Patients received selective intra-arterial infusions of cisplatin (150 mg/m2/wk for 4 weeks) and concomitant radiation therapy (2 Gy/fraction x 35 daily fractions over a 7-wk period) to the primary and clinically positive nodal disease. The patients were re-evaluated 2 months later and underwent salvage neck dissections if there was any residual disease. RESULTS: Classification of disease in the primary site was as follows: T1 in 2 patients, T2 in 6 patients, T3 in 14 patients, and T4 in 9 patients. Among the 31 patients who were assessed for response at the nodal site, 4 of 31 (13%) had a complete response, 21 of 31 (68%) had a partial response, and 1 of 31 (3%) had no response. Excluding the 5 patients who could not be evaluated, 4 of 26 patients (15%) had a complete response, 21 of 26 (81%) had a partial response, and 1 of 26 (4%) had no response. Nineteen patients subsequently underwent neck dissection, and five patients had histological evidence of residual disease. The remaining seven patients included four who had a complete response in their necks and three who died of intercurrent disease before re-staging. Among the 23 patients who were rendered disease free, there were no recurrences within the neck, whereas 1 patient had recurrence at the primary site and 11 patients had recurrence at distant sites. With a median follow-up of 15 months (range, 4-41 mo), the 3-year overall survival and disease-specific survival were 41% and 43%, respectively. CONCLUSIONS: Targeted chemoradiation therapy followed by surgical salvage is a highly effective approach for regional control of patients with N3 nodal disease, whereas additional strategies are required to address the problem of distant metastases.

Targeted chemoradiation for advanced head and neck cancer: analysis of 213 patients.

BACKGROUND: To determine the survival results, patterns of relapse, and organ preservation effects of a targeted chemoradiation protocol for patients with advanced (stage III-IV) carcinoma of the head and neck. METHODS: Analysis of 213 patients with stage III-IV squamous cell carcinoma treated at UT Memphis between June 1993 and March 1998. Treatment included weekly intra-arterial infusions of cisplatin (150 mg/m(2)/ week x 4) rapidly delivered to the tumor bulk, simultaneous intravenous thiosulfate for systemic drug neutralization, and conventional external-beam irradiation (180-200 cGy/fraction) to a total dose of 68-72 Gy. RESULTS: Tumor response, toxicity, disease control above the clavicle, pattern of relapse, and survival. There were 89 events of grade III-IV toxicity and 6 treatment-related deaths (grade V). Complete response in the primary and regional sites was obtained in 171 of 213 (80%) and 92 of 151 (61%), respectively. The rate of clearance of regional disease after neck dissection was 98%. There were 51 of 195 recurrences (26%): 11 local (5.6%), 5 regional (2.6%), and 35 distant (17.9%). The Kaplan Meier plot projections for overall and cancer-related 5-year survival was 38.8% and 53.6%, respectively, whereas disease control above the clavicle was 74.3%. CONCLUSIONS: We believe this chemoradiation protocol represents an effective management scheme for patients with advanced head and neck cancer with a high rate of organ preservation and possibly improved survival.

A feasibility study of salivary gland autograft transplantation for xerostomia.

BACKGROUND: Radiation-induced xerostomia is a frequent sequela in patients treated for cancer of the head and neck. One strategy to treat xerostomia would be to relocate portions of salivary tissue to adjacent submucosal sites that lie outside the radiation portals such as the anterior oral vestibule. It is not known whether salivary tissue transplanted as an autogenous free graft can survive, function adequately, and not produce mucoceles. METHODS: Salivary gland tissue from the parotid and submandibular glands of the Syrian hamster were transplanted into the submucosal layer of the cheek pouch. After 3 months of observation, looking at graft size, graft extrusion, ulceration, infection, and mucocele formation, the graft sites were harvested. The specimens then underwent pathologic analysis by hematoxylin and eosin staining, as well as immunohistochemical methods to determine positivity for cytokeratin, smooth muscle actin (SMA), and amylase. RESULTS: Histologic analysis of tissue harvested from Syrian hamsters grafted into the cheek pouch demonstrated intact, viable, organized salivary gland tissue. Eighty percent of the animals in the submandibular group and 63% of the animals in the parotid group had at least 1 graft with viable salivary tissue without undue complications. CONCLUSIONS: Salivary gland tissue can be transplanted successfully as free autogenous grafts in the Syrian hamster model. Further studies are needed to determine whether the grafts will subsequently become functional and whether growth can be biologically stimulated. This approach may be a useful strategy to protect salivary gland tissue in patients undergoing radiotherapy for head and neck cancer.

Concomitant radiation therapy and targeted cisplatin chemotherapy for the treatment of advanced pyriform sinus carcinoma: disease control and preservation of organ function.

BACKGROUND: Squamous cell carcinoma of the pyriform sinus is an unfavorable disease which frequently presents in advanced stages. Despite aggressive "standard treatment" involving debilitating surgery and postoperative radiation therapy treatments, the survival and functional outcome for pyriform sinus carcinoma remains poor. Hence, we reviewed our experience in the management of advanced pyriform sinus carcinoma using "organ preservation" chemoradiation therapy. METHODS: Twenty-five patients diagnosed with stage III/IV pyriform sinus squamous cell carcinoma treated with supradose, intra-arterial targeted cisplatin, and concomitant radiotherapy were analyzed for response rates, survival, pattern of failure, and function of the preserved organs. Our protocol consisted of weekly intra-arterial infusions of cisplatin at 150 mg/m(2) x 4 and concurrent radiation therapy at 1.8 Gy or 2.0 Gy/fraction to a planned total of 68-74 Gy to the primary site/overt nodal disease. RESULTS: Nineteen (76%) of the 25 patients were diagnosed with stage IV disease, 17 of whom were first seen with bulky lymphadenopathy (ie, N2-N3 disease) while 10 had T4 lesions. Twenty-four of 25 patients were evaluable for response assessment. Complete response rates of 92% and 76% were achieved at the primary site and in lymph nodes, respectively. Hence, the overall complete response rate in the neck was 76% (16/21). At a median follow up interval of 42 months (range = 30-58 months), the projected 5-year overall and disease-specific survival using the Kaplan-Meier method are 23% and 50% respectively. No patient has developed recurrence at the primary site and only one patient relapsed regionally, which was surgically salvaged for an "above clavicle" disease control rate of 88% and an organ preservation rate of 88%. Almost 90% of the patients have achieved a satisfactory voice and 70% are able to swallow at 12 months postcompletion of therapy. CONCLUSION: Our chemoradiation protocol is as effective as other treatment modalities for patients with advanced pyriform sinus carcinoma while maintaining organ preservation and function in the majority of the patients.

Quantitation of the change in GADD153 messenger RNA level as a molecular marker of tumor response in head and neck cancer.

Cells injured by exposure to cisplatin (cDDP) undergo a cellular injury response that shares characteristics with responses produced by many other injurious agents. We sought to determine whether the increase of the message of the "growth arrest and DNA damage-inducible" gene, GADD153, could be used to assess the extent of the cellular injury response in model systems and in patients with head and neck cancer after treatment with cDDP. The mRNA levels of GADD153, a gene highly transcriptionally activated by cDDP damage, were increased in a transient, concentration-dependent manner by cDDP when human UMSCC10b head and neck carcinoma cells were treated with cDDP both in vitro and when grown as tumor xenografts in nude mice. There was a good correlation between the change in level of GADD153 mRNA and UMSCC10b cell kill by cDDP in vitro (r = 0.98). The magnitude of the increase was proportionally reduced in UMSCC10b sublines that were 3- or 6-fold resistant to cDDP. GADD153 mRNA levels were measured in biopsies obtained before and 24 h after treatment with cDDP from 32 patients with stage III/IV head and neck cancer. There was a relationship between the increase in GADD153 mRNA levels and the response rate. Seven of the 32 patients had no response and no increase in GADD153 mRNA level. Among the eight patients who attained a partial response, the increase in GADD153 message ranged from 0.7-2.5-fold. In contrast, 17 of 32 patients had a complete response, and this was accompanied by a 2-9-fold induction of GADD153. The mean increase in the complete responders (3.8+/-2.2-fold) differed significantly from that for the partial responders (1.6+/-0.9) and nonresponders (0.8+/-0.5; P <0.05); the difference between the partial responders and nonresponders was also significant (P <0.05). An increase of GADD153 mRNA of 1.75-fold or higher predicted a complete response, with a sensitivity of 94% and a specificity of 87%. We conclude that the magnitude of the increase in GADD153 mRNA is a promising candidate for service as an intermediate marker of head and neck tumor response to cDDP. The fact that the change in GADD153 mRNA reflects the actual extent of injury sustained by the tumor makes it particularly attractive as a potential marker. One strength of this approach is that it can provide a measure of the effectiveness of therapy as early as 24-48 h after the first dose of treatment.

Efficacy of targeted chemoradiation and planned selective neck dissection to control bulky nodal disease in advanced head and neck cancer.

PURPOSE: To determine the efficacy of targeted chemoradiation with the radiation plus platinum (RADPLAT) protocol and planned selective neck dissection in patients with N2 to N3 nodal disease associated with upper aerodigestive tract carcinoma. METHODS: Analysis of 52 patients with N2a, N2b, or N3 disease involving 60 heminecks treated with intraarterial cisplatin, 150 mg/m2, and intravenous sodium thiosulfate, 9 g/m2, on days 1, 8, 15, and 22; radiation therapy, 180 to 200 cGy per fraction for 35 fractions (total dose, 68-74 Gy); and planned neck dissection (33 of 35 procedures were selective). RESULTS: Of the 56 evaluable heminecks, a clinical complete response was achieved in 33 (59%). Within this group, 16 neck dissections were performed, none of which yielded disease on pathological examination. A clinical partial response was obtained in 21 heminecks, of which 18 subsequently had a neck dissection, yielding disease on pathological examination in 14. In all cases, it was possible to completely excise all adenopathy with clear margins on pathological examination. The rate of regional disease control among the 56 evaluable heminecks was 91% (51/56) (median follow-up, 36 months). Four failures were associated with uncontrolled disease at other sites, and 1 was an isolated neck recurrence. CONCLUSION: Selective neck dissection appears to be an effective adjunct to targeted chemoradiation in controlling N2 to N3 neck disease.