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Biomedical subjects

K T Robbins

Publications and source records attributed to K T Robbins.

At least 37 records · Page 2Linked to original sources
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

Expanded application of selective neck dissection with regard to nodal status.

BACKGROUND: The efficacy of extending the application of selective neck dissection to include more-extensive neck disease in patients with squamous carcinoma of the upper aerodigestive tract remains controversial. METHODS: A review of all patients undergoing selective neck dissection at a single institution during a 5-year period was undertaken. The analysis was conducted on 82 patients who received 94 selective neck dissections as part of initial therapy for management of squamous carcinoma of the upper aerodigestive tract, including: oral cavity, oropharynx, larynx, and hypopharynx. RESULTS: Forty-six of the 94 dissected necks were supraomohyoid dissections, and 48 were lateral neck dissections. Sixty-five percent of patients were followed a minimum of 2 years and formed the cohort for final analysis. There were eight regional recurrences, three of which occurred in the contralateral, undissected neck. The regional recurrence rate for all patients undergoing selective neck dissection, with or without radiotherapy, according to pathologic N status was as follows: NO (1/33), 3%; N1 (1/8), 12.5%; and multiple positive nodes (3/26), 11.5%. A comparison of recurrence rates with respect to extent of neck disease (N0-N1 versus multiple positive nodes) for both types of neck dissection did not demonstrate significant differences; supraomohyoid neck dissection, p < .5; lateral neck dissection, p < .25. CONCLUSIONS: There exists an expanded role for selective neck dissection in selected patients with primary squamous cell carcinoma of the upper aerodigestive tract and multiple N+ cervical disease. The selection of patients who are candidates for selective lymphadenectomy should be based on pathoanatomic considerations with reference to the primary site of tumor and demonstrated level(s) of metastatic involvement.

Aged↗
PubMed1997

The predictive value of tumor regression rates during chemoradiation therapy in patients with advanced head and neck squamous cell carcinoma.

OBJECTIVE: The value of tumor regression rates in predicting survival outcome during chemoradiation therapy was prospectively evaluated. METHODS AND MATERIALS: Sixty-two patients diagnosed with locally advanced stage III/IV unresectable head and neck squamous cell carcinoma underwent weekly clinical and endoscopic serial assessment of primary and nodal tumor sizes during chemoradiation therapy between July 1993 and September 1995. Chemoradiation therapy consisted of protocol treatment using supradose intra-arterial targeted cisplatin (SIT-P) at 150 mg/m2 four times at weekly intervals along with intravenous sodium thiosulfate at 9 g/m2 and concurrent conventionally fractionated radiotherapy at 1.8 to 2.0 Gy/fraction (fx) to a total dose of 68 to 74 Gy. Tumor reduction was serially measured as a percentage of the original pretreatment size at weekly intervals by the same team of surgical and radiation oncologists. Correlations were then made between tumor regression rates and survival. RESULTS: Complete or near complete regression of disease during chemoradiation therapy as compared with nonresponsive/partially responsive disease was associated with better survival outcome (P = 0.001 and P = 0.013, respectively). Among patients exhibiting complete or near complete regression of disease, rapid tumor reduction (median = 4.2 weeks) was associated with inferior survival outcome when compared with slower disease regression (median = 6.4 weeks, P = 0.007). CONCLUSIONS: Our findings fail to support the "traditional" hypothesis that rapid tumor regression during treatment is predictive of an improved survival outcome. Treatment strategies that alter ongoing therapy based upon initial tumor regression rates should be avoided.

Antidotes↗
PubMed1996

A novel organ preservation protocol for advanced carcinoma of the larynx and pharynx.

OBJECTIVE: To pilot a targeted chemoradiation protocol for patients with advanced carcinoma of the larynx and pharynx that would circumvent upper aerodigestive tract dysfunction related to major oncologic surgery. DESIGN: Weekly intra-arterial infusions of supradose cisplatin (150 mg/m2 per week x 4) rapidly delivered to the tumor bulk, simultaneous intravenous sodium thiosulfate for systemic drug neutralization, and conventional external-beam irradiation (1.80-2.00 Gy per fraction x 35) were used. Between February 1991 and April 1994, 42 patients were treated who would otherwise have required a major resection of the tongue base, pharyngeal wall, or larynx. MAIN OUTCOME MEASURES: Tumor response, toxic effects, disease control above the clavicle, preservation of the larynx, maintenance of oral nutrition, and overall and disease-related 2-year survival. RESULTS: Three complications were related to the weekly transfemoral superselective intra-arterial procedures performed 160 times. Grade 3 to 4 chemotoxic effects were infrequent, occurring in 9 (5.5%) of 160 cycles, and only 1 patient required a radiotherapy break because of severe mucositis. A complete response in the primary site was obtained in 36 (86%) of 42 patients, 2 of whom had residual disease in the neck. Median follow-up was 13 months (range, 3-46 months). To date, there have been 5 recurrences: 2 regional and 3 distant. The 2-year overall and disease-related survival was 64% and 76%, respectively. The rate of disease control above the clavicle at 2 years was 86%. CONCLUSIONS: We believe this chemoradiation protocol represents an effective management scheme for patients with advanced head and neck cancer while minimizing dysfunction and possibly improving survival.

Adolescent↗
PubMed1996

Assessing vocal function after chemoradiation for advanced laryngeal carcinoma.

OBJECTIVE: To identify objective parameters that could serve as valid indicators of vocal function in evaluating patients treated at multiple centers for head and neck cancer. DESIGN: Objective measures of voice were validated against functional outcome measures of voice and communication. SETTING: A multidisciplinary university-based ambulatory head and neck cancer clinic. SUBJECTS: Fifteen patients at varying posttreatment intervals after chemoradiation therapy for head and neck cancer and 5 volunteers with no cancer but with a history of heavy smoking and drinking. MAIN OUTCOME MEASURES: Acoustic and aerodynamic parameters were measured in patients with head and neck cancer after treatment with combined chemotherapy and irradiation and in control subjects. Communicative function was assessed by perceptual assessment of recorded voice samples, by a clinician-based communication score, and by patient self-rating of voice and communication. RESULTS: Both perceptual analysis and communication score were concordant with patient self-rating of voice and communication ability. Acoustic measures were abnormal in patients, and jitter scores correlated with listener ratings of perceived voice quality. However, acoustic measures did not relate to communication function, as assessed by either the patient or the clinician. Laryngeal resistance demonstrated a significant correlation with both patient and observer assessments of voice quality and communication function. Laryngeal resistance was on average twice as high in patients who complained of voice fatigue, but this difference was not statistically significant. CONCLUSIONS: Laryngeal resistance, determined during standardized phonation, is a reliable objective parameter of vocal function after chemoradiation therapy for head and neck cancer. A standardized clinician-based communication scale holds promise as a useful tool. Acoustic measures reflect the sound of the voice but not the ability to communicate effectively.

Acoustics↗
PubMed1996

Targeted infusions of supradose Cisplatin with systemic neutralization for carcinomas invading the temporal bone.

In an attempt to improve the dismal prognosis for patients with advanced cancer involving the temporal bone, a regional chemotherapy technique was piloted as part of the multimodality therapy for such patients. Rapid supradose cisplatin infusions selectively delivered to the lesion were given to 14 patients with carcinoma involving the temporal bone. Concurrent systemic cisplatin neutralization was achieved with sodium thiosulfate which permitted the use of cisplatin dose intensity regimens equivalent to fivefold the conventional amount. Four patients received chemotherapy alone, four had concomitant irradiation, and six had subsequent irradiation and/or temporal bone surgery. All patients tolerated the chemotherapy without significant complications or toxicity.All three of the patients with previously untreated disease responded to chemotherapy (2 Crs, 1 PR); three of the seven patients with recurrent disease responded to chemotherapy; and all four patients treated with chemoradiation had a complete response (including one patient with recurrent disease). The median follow-up time was 19 months (range, 5 to 63 months). Nine of the 14 patients are alive, including the 4 who were treated with targeted chemoradiation.The use of targeted high-dose chemotherapy for patients with malignant skull base lesions offers hope for improved outcome, particularly when this regimen is given simultaneously with radiation.

Journal Article↗
PubMed1996

"Decadose" effects of cisplatin on squamous cell carcinoma of the upper aerodigestive tract. I. Histoculture experiments.

There is substantial laboratory and clinical evidence that solid tumors rapidly acquire cellular resistance to cisplatin. Experiments with human carcinoma cell lines and clonogenic assays indicate that resistance is usually mild to moderate and can be circumvented with higher concentrations of drug. The purpose of this investigation was to test this hypothesis with a histoculture assay of human upper aerodigestive tract (UADT) carcinomas. Using a sponge-gel supported histoculture, 43 tumor specimens from patients with squamous cell carcinoma (SCC) of the UADT were grown and exposed to cisplatin. Growth inhibition by the drug, in concentrations equivalent to peak therapeutic doses (1.5 micrograms/mL) and concentrations 10 and 25 times greater (15 and 37.5 micrograms/mL), were measured in specimens from patients with previously untreated and recurrent lesions. In vitro, the overall rate of sensitivity of the tumor samples to cisplatin concentrations of 1.5, 15, and 37.5 micrograms/mL were 22%, 62%, and 83%, respectively. In patients with previously untreated disease, the respective rates were 25.9%, 63.3%, and 79.3%, as compared with 10.0%, 55.6%, and 85.6%, respectively, for patients with recurrent disease. The response difference between cisplatin concentrations of 1.5 and 15 micrograms/mL was statistically significant. The "decadose" effect of cisplatin on growth inhibition was 2.44-fold for untreated lesions and 5.56-fold for recurrent tumors. The results indicate that resistance to standard doses of cisplatin by SCC of the UADT can be substantially overcome with a decadose (standard dose x 10) increase and is more pronounced in tumors from patients with recurrent disease. Progress toward improving survival of patients may be possible by incorporating decadose cisplatin therapy into a multimodality treatment plan.

Antineoplastic Agents↗
PubMed1996

"Decadose" effects of cisplatin on squamous cell carcinoma of the upper aerodigestive tract. II. Clinical studies.

There is evidence that solid tumors rapidly acquire cellular resistance to cisplatin. This resistance is usually mild to moderate and could be circumvented with higher concentrations of drug exposure if ancillary methods were available to avoid systemic cytotoxicity. The purpose of this study was to determine whether a tenfold increase in dose (decadose) would overcome cisplatin resistance. In a clinical trial, response effects of cisplatin at dose intensities ranging from 32.5 to 200 mg/m2 per week, which were delivered by highly selective intra-arterial infusions with a simultaneously administered intravenous neutralizing agent, were measured in 31 patients with squamous cell carcinoma (SCC) of the upper aerodigestive tract (UADT). The overall response rate (complete response [CR] and partial response [PR] to cisplatin therapy at dose intensity intervals of 0 to 74, 75 to 149, and 150 to 200 mg/m2 per week were 45.5%, 72.7%, and 100%, respectively. The average received dose intensities for nonresponders and responders (CR and PR) were 57.8 and 120.7 mg/m2 per week, respectively (P = .031). The results indicate that resistance to standard doses of cisplatin by SCC of the UADT, both previously untreated and recurrent, can be substantially overcome with "decadose" cisplatin therapy. Progress toward improving survival of patients with head and neck cancer, and possibly other site-specific malignancies, may be achieved by incorporating decadose cisplatin therapy into a multimodality treatment plan.

Adult↗