Search

Background. A phase II study was conducted using concurrent paclitaxel, carboplatin, and external beam radiotherapy (RT) in patients with advanced head and neck cancer. Methods. Forty-three patients (stage III, n = 12; stage IV, n = 31) were treated with 8 cycles of weekly paclitaxel (60 mg/m2), carboplatin (area under the curve [AUC] = 1), and RT (1.8 Gy daily; total dose, 66–72 Gy). Patients with initially palpable lymph nodes underwent neck dissection. Results. The overall clinical response rate was 91% (65% complete, 26% partial). Severe mucositis occurred in 37 (90%) patients, necessitating hospitalization in 13 (31%) patients. With a median follow-up of 49 months, the locoregional and distant failure rates were 26% and 21%, respectively. Conclusions. Concurrent paclitaxel, carboplatin, and RT for advanced head and neck cancer results in high complete response rates. Long-term follow-up has revealed the curative potential of this regimen, though the doses used resulted in unacceptable toxicity. © 2007 Wiley Periodicals, Inc. Head Neck 2008

background Preoperative chemotherapy or chemoradiation protocols are generally associated with high clinical response rates, but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel 60 mg/M2, and carboplatin (AUC of 1) plus concurrent fractionated external beam radiation (45 Gy) followed by organ-preserving (or function restorative) surgery when applicable to maximize local-regional tumor control. patients and methods Operable patients staged by triple endoscopy received a percutaneous endoscopic gastrostomy and vigorous dental and nutritional support during therapy. Weekly paclitaxel 60 mg/M2, carboplatin (AUC of 1), and radiation 45 Gy were given with rebiopsy of the primary site at 5 weeks. Patients with positive biopsy had definitive surgery in 4 to 5 weeks. Patients with negative biopsy-results received 3 additional weeks of radiation, to a total dose of 72 Gy plus carboplatin and paclitaxel. results The 35 patients were 29 men and 6 women, aged 40 to 71 years, with stage III (12) or stage IV (23) cancer. The site of the cancer was oral cavity, 10; base of tongue, 3; oropharynx, 3; hypopharynx, 4; larynx, 12 (glottic, 6; supraglottic, 6), unknown primary, 2; other, nasal cavity, 1. Of 34 evaluable patients, 16 (47%) had a complete clinical response (CR) and 18 (53%) had a partial response (PR); total clinical response rate was 100%. A pathologic CR at the primary site occurred in 23 of 34 patients (68%; 2 had an unknown primary) who went on to completion radiation at 67 to 72 Gy. After induction chemoradiation 21 patients with N1-3 nodes had neck dissection; 6 (31%) had positive nodes. Twelve patients had residual cancer at the primary site at time of rebiopsy: mandible, 4; maxilla, 1; base of tongue, 2; larynx, 4; floor of mouth, 1; and nasal cavity, 1. All were resected with function-preserving reconstruction. At median follow-up of >12 months, progression-free and overall survivals were 71% and 83%, respectively. conclusion Preoperative treatment with paclitaxel, carboplatin, and radiation is associated with high CR at the primary site and a high level of organ preservation or functional restoration if ablation is done.

The long-term outcomes of selective organ preservation in operable, locally advanced head and neck cancers in two sequential chemoradiotherapy (CRT) protocols (HN-53, HN-67) are reported. A total of 65 patients were treated with CRT consisting of carboplatin (AUC = 1/week) and paclitaxel (60 or 40 mg/m2/week) with radiation (1.8 Gy/day). After 5 weeks of CRT, if primary site biopsies were pathologically negative, then completion CRT to 67–72 Gy was done with neck dissection in node-positive cases. Alternatively, a positive rebiopsy required primary site resection and neck dissection followed by radiotherapy boost as deemed necessary. Pathologic complete responses occurred in 71% patients who then completed CRT; the remaining 29% patients underwent primary site surgery. The 5-year and median overall survival were 47% and 57 months with no statistically significant differences between the two groups. Overall long-term failure rates were: 6% local, 6% regional, and 32% distant. This strategy of selective organ preservation was effective in 71% patients with CRT, whereas salvage surgery was required in the remainder. Long-term survival was equivalent in both treatment groups.

Objective: Inhalation injury can permanently alter normal laryngeal function. The aim of this study was to examine the early changes in voice, swallowing, and breathing in laryngeal inhalation injuries. Study Design: This was a prospective analysis of nine patients with inhalation injuries at a tertiary care institution. Methods: Laryngeal function of patients admitted for inhalation injury requiring intubation was documented using videostroboscopy and swallowing evaluation by the speech pathology service. Bronchoscopy was used to classify the degree of inhalation injury. Association among total body surface area, facial burns, severity of laryngotracheal injuries, and loss of function was attempted. Results: All three patients with severe tracheal inhalation injury presented persistent hoarseness at 1-year follow up with abnormal videostroboscopy findings. No association was found between inhalation injury and total body surface area burned. None of the patients in this series presented permanent swallowing dysfunction. Conclusion: The otolaryngologist plays an important role in the initial and long-term management of inhalation injuries. Inhalation injuries should be managed in a multidisciplinary fashion. There may be a correlation between the degree of tracheal injury and laryngeal injury and hoarseness.

Preoperative chemotherapy and chemoradiation protocols are generally associated with high clinical response rates but limited pathologic responses for large primary tumors. We have initiated a prospective phase II study of weekly paclitaxel and carboplatin plus concurrent, fractionated external-beam radiation, followed by organ-preserving or function-restorative surgery (when applicable to maximize locoregional tumor control). Operable patients staged by triple endoscopy received a percutaneous gastrostomy and vigorous dental and nutritional support during therapy. Paclitaxel 60 mg/m2 and carboplatin at an area under the concentration-time curve of 1 were administered weekly with radiation therapy 45 Gy, with repeat biopsy of the primary site at 5 weeks. Patients with a positive biopsy had definitive surgery within 4 to 5 weeks. Patients with a negative biopsy received 3 additional weeks of radiation therapy, to a total dose of 72 Gy plus paclitaxel and carboplatin. Forty-three patients were enrolled, including 33 men and 10 women ranging in age from 37 to 81 years. Fourteen patients had stage III disease, 19 patients had stage IVA disease, and 10 patients had stage IVB disease. Sites of disease included the floor of the mouth (n = 8), tongue (n = 8), oropharynx (n = 5), hypopharynx (n = 4), larynx (n = 12), palate-tonsil (n = 2), unknown primary (n = 3), and nasal cavity (n = 1). Of 38 patients evaluable for primary response (two patients had unknown primary tumor, two patients failed to complete the chemoradiation protocol, and one patient was evaluable for toxicity only), 18 patients had a complete clinical response and 20 patients had a partial response; the overall clinical response rate was 100%. A pathologic clinical response at the primary site occurred in 25 of these 38 patients (66%), who subsequently received completion radiation (67 to 72 Gy). After induction chemoradiation, 36 patients with N1-N3 nodes had neck dissection; seven had positive nodes (19%). Fourteen patients had residual cancer at the primary site at the time of the repeat biopsy. Sites of the lesions were the floor of the mouth/mandible (n = 4), nasal cavity/maxilla (n = 2), base of tongue (n = 2), and larynx (n = 6). All were resected with function-preserving reconstruction (two patients required total laryngectomy and one patient refused surgery). At a median follow-up of more than 16 months, progression-free and overall survival rates were 64% and 68%, respectively. Preoperative paclitaxel, carboplatin, and radiation was associated with a high clinical response rate at the primary site and a high level of organ preservation or functional restoration, if ablation was performed.

The beneficial effects of chemotherapy in patients with advanced head and neck cancer remain controversial in terms of survival, but have shown some promise in improving locoregional control and quality of life. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel and carboplatin with concurrent conventional fractionated external-beam radiotherapy. Paclitaxel and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, cell blockage in G2/M phase and inhibition of DNA repair, respectively. Patients were stratified as either operable or inoperable. This report pertains to the inoperable patient group, who received eight cycles of weekly paclitaxel (60 mg/m2), carboplatin (area under the concentration-time curve of 1) with conventional radiotherapy (72 Gy). Chemoradiotherapy was followed by neck dissection for those patients who presented with clinically palpable lymph nodes. Thirty-three patients were enrolled in this group (23 men and 10 women with a median age of 56 years). Eleven patients (33%) had stage III disease; 22 (67%), stage IV disease. The median follow-up period was 14 months. Clinical complete response occurred in 20 patients (60%) and partial response occurred in 10 (30%), for an overall response rate of 90%. Following completion of therapy, 18 patients have undergone biopsy at the primary tumor site and 17 were negative. Eight of the 16 patients with clinically palpable neck nodes at presentation underwent neck dissection; five (63%) had negative nodes. Mucositis was the most common toxicity. Grade 3 or 4 mucositis occurred in 30 of the 33 (90%) patients. Other grade 3 or 4 toxicities included skin (22%), candidiasis (19%), neutropenia (9%), and dehydration (6%). One patient with laryngeal carcinoma who had pathologic complete response developed cartilage necrosis and is undergoing hyperbaric oxygen therapy. Survival data are early but encouraging. Concurrent paclitaxel, carboplatin, and external-beam radiotherapy yielded excellent clinical and pathologic responses. Mucositis remains the most common and significant morbidity. The study will continue for necessary accrual.

Radiotherapy or surgery alone for advanced head and neck cancer generally yields poor results. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, namely, blocking the cell cycle in the G2/M phase and inhibiting DNA repair. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel 60 mg/ml and carboplatin (area under the concentration-time curve of 1), each given as a single dose weekly with concurrent conventional fractionated external beam radiotherapy. Patients were stratified into two groups: operable and inoperable/unresectable. The operable and inoperable groups received 5 weeks (45 Gy) and 8 weeks (72 Gy) of chemoradiotherapy, respectively. Patients in the operable group were evaluated with repeat biopsies from the primary site after 5 weeks. Those with a positive biopsy underwent surgery; those with a negative biopsy received 3 additional weeks of chemoradiotherapy. Thirty-four patients were entered in the operable group (28 men and six women; 40 to 71 years of age; 12 stage III and 22 stage IV). Of 26 evaluable patients, 19 (73%) had a complete clinical response (95% confidence interval [CI], 52% to 88%) and six (23%) had a partial response (95% CI, 9% to 44%), for a total clinical response rate of 96% (95% CI, 80% to 100%). A pathologic complete response at the primary site (two had an unknown primary site) occurred in 17 of 24 (71%) patients (95% CI, 49% to 87%). Of 20 patients with N1-3 nodes who underwent neck dissection, 17 (85%) had pathologically negative lymph nodes. Seven patients with residual tumor at the primary site were resected (oral cavity, three; maxilla, one; base of tongue, one; and larynx, two). Grades 3 and 4 mucositis were seen in 19 (73%) patients; mucositis was the most common and significant morbidity. Accrual for the inoperable group continues. Concomitant paclitaxel, carboplatin, and external beam radiotherapy yielded excellent clinical responses, but produced significant grade 3/4 toxicity. In the operable group, the majority of responders had a complete pathologic response. These preliminary findings will be assessed in terms of response duration, organ preservation, and long-term survival.

The limiting factors in conventional cytogenetic analysis of cell culture, especially of solid tumors, include insufficient metaphases, overgrowth of abnormal mitotic cells by normal cells, and suboptimal quality of harvesting and banding. Despite the availability of numerous protocols to induce G-banding, as well as Q-, R-, and C-banding, occasions still arise in which the analysis is severely limited by these factors and incomplete conclusions are often drawn as to the precise nature of the chromosomal abnormality, if indeed any can be detected. By adopting a rational approach of (1) close monitoring of cultures and rapid harvesting as soon as it is feasible, and (2) analysis of available metaphases by a combination of the GTG technique, fluorescent in situ hybridization (FISH), and chromosome morphometry using a graphic arts tool, a significant improvement in success rate may be more readily achieved. Here pathological and cytogenetic data are presented of a case of parotid gland carcinoma ex mixed tumor with the karyotype of 46, XX, del(5)(q12), dir ins(8;5)(q12;q12qter), add(12)(p13)/46, XX. This case is utilized to illustrate the importance of application of our combined strategy.

6042 Background: A consecutive series of neoadjuvant protocols has focused on restaging re-biopsy to select therapy of Stage III/IV squamous cancer since 1995. Patients with positive restaging biopsy have subsequent resection whereas those having a negative re-biopsy have completion chemo- radiation therapy of primary site to total dose 68–72cGy. We are currently reporting the benefit of giving induction chemotherapy prior to chemoradiation. Methods: Initial protocols (H&N 53& 67) utilized concurrent preoperative Paclitaxel (P) (60mg/M² or 40mg/M2) + Carboplatin (AUC) + RT (45G) 67(64 evaluable pts). Subsequent studies (H&N79) utilized induction chemo (P 135mg/M², C (2AUC) weekly x 6 followed by chemoradiation therapy P 40 C (1AUC) + 45 Gy (H&N79) 32 pts (13 operable). Results: Protocols, 53 & 67 induced a complete pathologic response in 70% vs. a 52% clinically determined CR permitting completion radiation with primary site preservation. Neck dissection (ND) revealed persistent disease in 37% confirming ...

8549 Background: Timing and frequency of non occlusive (nO) or occlusive (O) CVCrT in cancer patients (pts) remain unclear. In this randomized controlled trial we studied these points and evaluated the efficacy and safety of short-term prophylaxis with A or D in the prevention of CVCrT. Methods: Consecutive cancer pts without contraindications to short-term anticoagulation, scheduled for chemotherapy via CVC, were randomly assigned to receive: A 1 mg/day for 3 days before and 8 days after CVC insertion; D 5,000 IU 2 hours before and daily for 8 days after CVC insertion; no anticoagulant treatment (NT). All pts underwent venography (V) at day 8 and 30 after CVC insertion and then every two months until CVC removal . The primary endpoint was V detected CVCrT, evaluated as nO or O when it was partially or completely occlusive of the vein lumen, respectively. Bleeding episodes were recorded. Proportions were compared using chi-square test together with odds ratio (OR). Results: 450 pts were randomized, 348 of whom (120/150 A, 114/150 D, and 114/150 NT) underwent V (median number of procedures 4, range 2–8). Both A and D reduced the frequency of V detected CVCrT (21.9% A vs 55.3% NT, OR= 4.35 (95% CI 2.43–7.69), p No significant financial relationships to disclose.

This pilot study for resectable stage III and stage IV squamous cell carcinoma of the head and neck used a cytoreduction phase of preoperative radiation with cisplatin, followed by an eradicative treatment phase with radical surgery (group 1) or radical dose radiation and cisplatin (group 2), followed by adjuvant chemotherapy with 5-fluorouracil infusion and cisplatin delivered at 4-week intervals for six cycles following initial radiation therapy to the primary site. A total of 43 patients were treated between January 1984 and January 1987; 14 were classified with stage III carcinoma, 28 with stage IV, and one patient was not staged. Out of 43 patients, two did not complete therapy. Forty-one patients completed the eradicative phase of treatment. Complete tumor clearance at the end of the eradicative treatment phase was 88% (36 of 41 patients), 95% (18 of 19) in group 1 and 82% (18 of 22) in group 2. Actuarial recurrence-free survival was 61% at 3 years. Among 36 patients with complete tumor clearance after the eradicative treatment phase, there was no statistically significant difference for overall and recurrence-free survival between group 1 and group 2. In general, toxicity was not excessive, although mucositis, weight loss, and hematologic and neurologic toxicity were observed in varying degrees in these patients.

We have a 67-year-old Caucasian male presenting with a (T4, N1b, Mo) Stage III squamous cell carcinoma of the larynx. He subsequently underwent a total laryngectomy and right radical neck dissection. It was only determined by the pathology report that the cervical nodes in the neck specimen obtained the associated disease, Hodgkin's (mixed cellular lymphoma), rather than the expected well differentiated squamous cell carcinoma found in the larynx. Metastatic work-up was unrevealing. Reviewing the English literature fails to reveal a similar case report of squamous cell carcinoma of the larynx with Hodgkin's disease in the associated neck dissection. It was unfortunate that this patient died of a third pathology, cerebral hemorrhage, in the immediate post-op period.

\def\tpc{three-particle correlation} \def\twopc{two-particle correlation} Measurements are presented of short range three-particle correlations in e^+ e^- annihilations at LEP using data collected by the DELPHI detector. %The jet structure is studied using three-particle correlation functions. At small values of the four-momentum difference, strong three-particle correlations are observed for like-sign (+++ and ---) and for unlike-sign (++- and +--) pion combinations which are not a consequence of two-particle correlations. A possible explanation of the observed effects in like-sign combinations is the existence of higher order Bose-Einstein interference, which significantly changes the particle distributions in jets.