The evolving role of combined modality therapy in head and neck cancer.
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Combined Modality Therapy↗
Biomedical subjects
K T Robbins
Publications and source records attributed to K T Robbins.
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.
Animals↗
Integrating radiological criteria into the classification of cervical lymph node disease.
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Head and Neck Neoplasms↗
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.
Adult↗
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.
Aged↗
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.
Animals↗
Postoperative wound infection in head and neck oncologic procedures.
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Head and Neck Neoplasms↗
The effects of radiation on craniofacial skeletal growth: a quantitative study.
To determine whether radiation delivered to children treated for head and neck cancer causes deformity, we performed a quantitative analysis for craniofacial asymmetry. A total of 42 patients, with either rhabdomyosarcoma or nasopharyngeal carcinoma, treated between 1980 and 1991, were analyzed. Exclusions included 16 subjects, leaving 26 children of mixed race and gender with a median age at diagnosis of 13 years (range: 2-18) and a median age at follow-up of 4 years (range: 3-37). Data from 14 measurements of the cranium and facial skeleton, for which normative data exist, were recorded. Symmetry of the face and head were determined and each measurement was compared to age specific standards. Deviation occurred in the cranial vault, the anterior and mid-interorbital distances and lateral orbital wall length. Asymmetry existed in the medial and lateral orbital wall lengths and the zygomatic arches. We conclude that, children irradiated for head and neck malignancies, have significant alterations in some skeletal measurements indicative of treatment induced asymmetry and potential deformity.
Adolescent↗
Eating and weight changes following chemoradiation therapy for advanced head and neck cancer.
OBJECTIVE: To describe the functional outcomes of weight loss and eating following a targeted chemoradiation protocol consisting of a selective supradose of intra-arterial cisplatin (150 mg/m2 per week for 4 weeks) with parenteral sodium thiosulfate and external-beam irradiation (1.8-2.0 Gy per fraction per day for 35 days). SUBJECTS AND DESIGN: Forty-seven patients with advanced head and neck cancer treated with a targeted chemoradiation protocol were monitored for weight and eating status before treatment and as long as 18 months after treatment. RESULTS: A statistically significant weight loss (P<.001) occurred during the targeted chemoradiation protocol, with a mean weight ratio of 90% of the starting weight. The ability to eat also declined, with an increase in reported swallowing difficulties and a need for percutaneous endoscopic gastrostomy tubes from 4 (9%) to 12 (26%). There were no significant changes in weight after the initial weight loss. Tumor stage and nodal involvement had no effect on weight loss. At the start of treatment, 18 patients (38%) reported normal eating and 4 (8%) required a feeding tube. By 18 months after treatment, 41 (87%) were eating normally, 34 (72%) reported normal eating, and 6 (13%) required a percutaneous endoscopic gastrostomy tube. CONCLUSIONS: Patients undergoing a targeted chemoradiation protocol for head and neck cancer lost about 10% of their pretreatment weight and had a decline in eating ability. Difficulty swallowing during the treatment may be due to adverse effects such as mucositis and nausea. By 18 months after therapy, most were able to eat normally and maintain their weight.
Adult↗
Acute and chronic changes in swallowing and quality of life following intraarterial chemoradiation for organ preservation in patients with advanced head and neck cancer.
BACKGROUND: Health-related quality of life (QOL) provides a measure of the patient's perception of his life after treatment. This study was undertaken to assess changes in QOL and swallowing in patients undergoing concurrent chemoradiotherapy (CR) for head and neck cancer. The assessment tools consisted of the Head and Neck Radiotherapy Questionnaire (HNRQ) and a swallowing questionnaire (SQ). METHODS: The HNRQ and SQ were administered to a group of CR patients prior to treatment (n = 58), after the last week of treatment (n = 37), and 6 months after treatment (n = 27). Weight change was monitored in treatment subjects. RESULTS: The results indicate that QOL and swallowing function decrease acutely during CR (p < .05) but improvement begins shortly after the treatment-related decline. At 6 months after CR, mean QOL exceeds pretreatment level. The oropharynx patients have the poorest outcome when compared with laryngeal and hypopharyngeal patients. A stronger correlation exists between swallowing and QOL at 6 months post-CR than during treatment (R = .52 versus R = .30). CONCLUSIONS: Quality of life and swallowing are compromised in advanced head and neck cancer patients prior to treatment. There was a further decrease in QOL and swallow function during CR. Organ-preservation programs in head and neck cancer result in improved QOL and swallowing 6 months after treatment. The degree of improvement is site-specific.
Acute Disease↗
Classification of neck dissection: current concepts and future considerations.
In response to the increased number of neck dissection procedures and the lack of uniformity of terminology for describing these, several classification proposals have been made. The consensus report on neck dissection terminology by the American Academy of Otolaryngology-Head and Neck Surgery seems to have gained wide acceptance. This report outlines the Academy's classification system and its definitions for the lymph node groups. Other authors contributions are discussed and recommendations are suggested for future refinements to the classification system.
Head and Neck Neoplasms↗
Management of the neck in patients with head and neck cancer treated by concurrent chemotherapy and radiation.
The current high level of interest in organ preservation strategies for patients with advanced squamous cell carcinoma of the head and neck undoubtedly will result in increasing numbers of patients managed initially with chemotherapy and radiation, either sequentially or concurrently. In some protocols, surgery, and neck dissection in particular, will either be mandatory or offered based on the degree of response to treatment and initial stage of neck disease. Head and neck oncologic surgeons need to be involved and at the forefront of such trials, to allow meaningful data regarding pathologic response to treatment to be obtained, as well as to define the role of surgery in such patients. Although present data is limited, it would appear that in patients achieving a complete response to chemoradiation, the role of neck dissection may be more limited than in the past, even for patients with N2 to N3 neck disease at presentation. Surgical complications may be increased in this heavily treated patient population, and subsequent surgery should be designed to minimize the risk of wound complications, especially if performed before the patient has made a full recovery from the metabolic and immunologic derangements associated with chemoradiation. Head and neck surgeons need to play an active role in the design and conduct of chemoradiation trials so that these and other relevant questions will be answered by the data generated.
Antineoplastic Agents↗
Isolated mucoepidermoid carcinoma in the neck.
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Adenoma, Pleomorphic↗
Observations on control of N2 and N3 neck disease in squamous cell carcinoma of the head and neck by intra-arterial chemoradiation.
Patients with head and neck squamous cell cancer with N2 and N3 neck disease have a poor prognosis and are at risk to fail regionally despite combined surgery and radiation. Twenty-two patients with N2 and N3 neck disease (and T3-4 primaries) were treated with intra-arterial, high-dose cisplatin (CDDP), 150 mg/m2 per week for 4 weeks, and concurrent radiation. All patients were followed for at least 2 years or until death from any cause. Twenty patients had a complete response at the primary site. Two of the 20 with a complete response later had a neck recurrence and died. Five patients with palpable nodes after treatment underwent fine-needle aspiration (FNA), one of which was positive and two suggestive of cancer. Six neck dissections were performed in this group, only two of which had positive nodes. This chemoradiation protocol may offer reasonable control of N2 and N3 neck disease in advanced head and neck squamous cell cancer. Neck dissection appeared to be necessary in only those patients with nodes 8 weeks after treatment in whom FNA was positive or suggestive of cancer. Because of the relatively small size of this series, additional accrual and monitoring of such patients is planned.
Adolescent↗
An organ-preserving selective arterial chemotherapy strategy for head and neck cancer.
PURPOSE: Squamous cancer of the upper aerodigestive tract is a disheartening disease. Despite our best efforts, the long-term survival rate remains only 15% to 40%, and surgical cures often decrease the quality of life owing to the loss of swallowing and speech organs. A better understanding of tumor dynamics and the discovery that thiosulfate can neutralize cisplatin led us to develop a treatment plan that combines a rapid superselective high-dose intraarterial delivery of cisplatin (CDDP), simultaneous intravenous infusion of its antagonist, thiosulfate, and radiation therapy. METHODS: Patients with advanced head and neck squamous cancer were entered into the protocol after a multidisciplinary evaluation that included CT or MR imaging. Forty-two patients constituted the first cohort. After baseline angiography, an arterial acceptance test determined the maximum infusion rate that the tumor's nutrient artery would accept. CDDP was then infused at that rate, usually within 3 to 5 minutes, while the antagonist thiosulfate was given intravenously. In the second cohort of 85 patients with stage 3 or 4 previously untreated and unresectable disease, local radiation was added to the treatment plan. The radiation dose (180-200 cGy/d x 35) was delivered regionally on the basis of the known radiosensitizing effect of CDDP. RESULTS: Cohort 1 allowed us to develop the infusion technique and to establish a dose quantity and delivery frequency. When 150 mg/m2 was administered weekly for 4 weeks, no severe toxicity was found. In cohort 2, 72 (92%) of the remaining 78 patients had complete disappearance of their tumor. Seventeen severe toxic events were associated with 323 femoral catheterizations. One patient died of pulmonary embolus, precluding follow-up evaluation. Six patients had neurologic sequelae, three with transient and three with permanent strokes. CONCLUSION: Rapid superselective chemotherapy with CDDP combined with a circulatory systemic antagonist allowed delivery of an antitumoral drug directly into the lesion while protecting the kidneys and bone marrow from the agent's systemic effects. Use of a dose regimen of 150 mg CDDP/m2 per week for 4 weeks resulted in the disappearance of a large percentage of advanced squamous cancers.
Antineoplastic Agents↗
Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer: the Memphis experience.
PURPOSE/OBJECTIVE: To evaluate the feasibility, response rates, and toxicity of a Phase II study using targeted supradose cisplatin and concurrent radiation therapy in unresectable Stage III-IV head and neck squamous cell carcinoma. METHODS AND MATERIALS: Sixty patients presenting between 6/93-9/94 were enrolled, 44 (73%) of whom had T4 and/or N2-N3 nodal disease. All patients were treated with rapid targeted superselective intraarterial infusions of cisplatin (150 mg/m2 weekly x 4) and simultaneous sodium thiosulfate intravenously (9 g/m2) for systemic neutralization of cisplatin. Concurrent (day 1) daily radiation therapy was delivered to the primary tumor and overt nodal disease to 66-74 Gy while the uninvolved lower neck received 50 Gy, at 2.0 Gy/fraction. RESULTS: Fifty-one (85%) patients completed the full RADPLAT protocol as planned. Fifty-seven of 60 patients were evaluable for response. Histological (n = 50) or clinical (n = 7) assessment of primary site revealed a complete response (CR) in 52 patients, partial response (PR) in 4, and stable disease (SD) in 1. Of the 40 patients presenting with nodal metastases, pathological (n = 31) or clinical (n = 6) assessment revealed a CR in 25, PR in 11, and SD in 1, while 3 were unevaluable. Overall, for both primary site and nodal disease, CR was attained in 44 (75%), PR in 12 (23%), and SD in 1 (2%) of the 57 evaluable patients. Only 2 (4%) of 57 evaluable patients have recurred above the clavicle, 1 in the primary site and 1 in the regional lymph nodes. Twelve patients (23%) have failed in distant sites. Grade III/VI toxicity has included gastrointestinal in 6, hematologic in 6, mucosal in 12, vascular in 4, and neurological in 4 patients. CONCLUSION: Concurrent radiation therapy and targeted supradose cisplatin (i.e., RADPLAT) can be safely delivered with high response rates and excellent loco-regional control in advanced Stage III/IV head and neck squamous cell carcinoma.
Adult↗
Ototoxic effects of supradose cisplatin with sodium thiosulfate neutralization in patients with head and neck cancer.
OBJECTIVE: To assess the incidence and magnitude of ototoxicity in patients undergoing an experimental targeted chemoradiation protocol incorporating extremely high-dose intra-arterial cisplatin therapy with systemic sodium thiosulfate neutralization for the treatment of advanced carcinomas of the head and neck. DESIGN: Inception cohort study. SETTING: University-based, tertiary care referral center for advanced head and neck malignant disease. PATIENTS: The first 70 patients with advanced carcinomas of the head and neck consecutively entered in the protocol. INTERVENTION: Patients received up to 4 weekly courses of intra-arterial cisplatin (150 mg/m2 per infusion), together with systemic sodium thiosulfate and external beam radiation (68-70 Gy). Audiometric analysis was performed before the initiation of therapy, and subsequent to the second and fourth cisplatin infusions. MAIN OUTCOME MEASURES: Audiometric thresholds. Ototoxicity was defined as an increase in pure-tone threshold of 15 dB at 1 frequency or 10 dB at 3 frequencies, between 250 and 4000 Hz. RESULTS: The incidence of ototoxicity was 25% at 150 mg/m2, 50% at 300 mg/m2, 64% at 450 mg/m2, and 60% at 600 mg/m2. Hearing at frequencies of 2000 Hz or less was minimally or not affected. Previous hearing loss did not appear to affect the incidence of ototoxicity. A plateau of hearing loss at 60-dB hearing level, as noted by other authors, was not observed. There were no cases of debilitating tinnitus or of vestibular loss. CONCLUSIONS: Ototoxicity did occur but was largely confirmed to the higher frequencies. Hearing losses resulting from this chemoradiation protocol were not sufficiently severe to alter its application.
Adult↗