Carboplatin (CBDCA) and radiotherapy for stage IV carcinoma of the head and neck: a phase I-II study

The prognosis of patients with squamous cell carcinoma (SQC) of the head and neck (H&N) depends on the primary site and anatomical extent of the disease. Recurrence rates after conventional surgery (S) and/or radiotherapy (RT) remain low for localized tumors, whereas in advanced loco-regional disease they occur in over 60% of all cases. Several combinations of treatment modalities have been attempted in order to improve local control in Stages III and IV. Unfortunately, the recurrence rate remains high with added morbidity when conventional surgery is combined with pre or post-operative radiotherapy. Induction chemotherapy (CT) with Cisplatinum and Bleomycin has resulted in severe toxicities when combined with radiotherapy. To evaluate the toxicity of Carboplatin (CBDCA), a second generation platinum analog, when given simultaneously with conventional doses of radiotherapy, 26 patients with Stage IV SQC of the head and neck were treated at the University of Maryland Medical Systems. There were 23 males and 3 females; median age was 59 years and median Karnofski performance status was 60. Twenty patients had received no prior therapy; six had surgical exploration and excision with measurable residual disease. Anatomically, six patients had tumors of the oral cavity, twelve in the pharynx, one in the nasopharynx, four in the larynx, one in the hypopharynx, one in the maxillary antrum, and one was an unknown primary. These patients were treated as out-patients with weekly injections of Carboplatin. The dose was escalated: two patients received 60 mg/M2, seven received 75 mg/M2, thirteen were treated with 100 mg/M2, and four with 400 mg/M2. The radiotherapy was given daily with conventional fractions of 180 cGy and total tumor doses of 60-75 Gy. Toxicities were mainly hematological with median nadirs decreasing with increasing doses of Carboplatin. Mucositis was seen in over 80% of the patients, but interestingly enough, it has never been more severe than that observed with radiotherapy alone. So far, there has not been any kidney, ear, or neurotoxicities. Of 25 evaluable patients, 19 (76%) responded with 13 (52%) showing complete response. The overall median survival time is 266+ days (324+ for responders and 179+ for non-responders). The follow-up is still short, 10-14 months, but 9 of 13 patients with complete response have not yet progressed.     

Concomitant boost radiation and concurrent cisplatin for advanced head and neck carcinomas. Preliminary results of a phase II, single-institutional trial

INTRODUCTION: This study aims to asses the effectiveness and toxicity of boost radiotherapy concomitant and concurrent cisplatin for patients with locally advanced head and neck cancer (LAHNC). MATERIAL AND METHODS: There were 30 patients included in a prospective, phase II single-institution trial and of whom, 29 were at AJCC stage IV and 1 at stage III. Treatment consisted of radiotherapy acceleration fractionation with concomitant boost, 72 Gy, and 2 cycles of concomitant cisplatin (20 mg/m2/day continuous infusion; days 1-5 and 29-33). Amifostine, (i.v. 200 mg/m2) was administered to 26 prior to the first fraction of radiotherapy. Endpoints of the study were quality-of-life (QL), overall survival, and local control of disease. RESULTS: Complete response (CR) was achieved in 23 patients (77%), 2 patients had partial response (PR) (7%), 4 had no response (13%), and 1 was not evaluated for response. The 2-year overall survival and loco-regional control were 60% and 56%, respectively. Main toxicity was grade 3 or 4 mucositis in 93% of the patients. QL scores (questionnaire QLQC30; version 3.0) and the HN cancer module QLQ-HN35) showed a worsening in areas related to the treatment e.g. dry mouth, problems stretching the mouth, and sticky saliva. CONCLUSIONS: this combination modality is active, but toxic, in the treatment for LAHNC. Concomitant boost radiotherapy is probably, not the best radiotherapy schema for combining with chemotherapy in LAHNC.     

Mature results of a phase III randomized trial comparing concurrent chemoradiotherapy with radiation therapy alone in patients with stage III and IV squamous cell carcinoma of the head and neck

BACKGROUND: The current study presents mature results from a Phase III randomized trial comparing radiation therapy and concurrent chemoradiotherapy in patients with resectable American Joint Committee on Cancer Stage III and IV disease. METHODS: One hundred patients were randomized to receive either radiation therapy alone (Arm A) (at a dose of between 66-72 grays [Gy] at 1.8-2 Gy per day) and the identical radiation therapy with concurrent chemotherapy (Arm B) (5-fluorouracil, 1000 mg/m(2)/day, and cisplatin, 20 mg/m(2)/day, both given as continuous intravenous infusions over 4 days beginning on Days 1 and 22 of the radiation therapy). Primary site resection was planned for patients with residual or recurrent local disease. Cervical lymph node dissection was performed for regional persistent disease or recurrence, or if N2-3 disease was present at the time of presentation. RESULTS: After completing all therapy including surgery, 82% of the patients in Arm A and 98% of the patients in Arm B had been rendered disease free (P = 0.02). At a median follow-up of 5 years (range, 3-8 years), the 5-year Kaplan-Meier projections for overall survival for Arm A versus Arm B were 48% versus 50% (P = 0.55). Kaplan-Meier projections for the recurrence free interval were 51% versus 62% (P = 0.04), projections for a distant metastasis free interval were 75% versus 84% (P = 0. 09), projections for overall survival with primary site preservation were 34% versus 42% (P = 0.004), and projections for local control without surgical resection were 45% versus 77% (P < 0.001). Salvage surgery proved to be successful in 63% and 73%, respectively, of the Arm A and Arm B patients with primary site failure. Unrelated death while free of disease occurred in 22% and 32%, respectively, of Arm A and Arm B patients (P = 0.26). CONCLUSIONS: The addition of concurrent chemotherapy to definitive radiation in patients with resectable Stage III and IV squamous cell carcinoma of the head and neck improves the likelihood of disease clearance, a recurrence free interval, and primary site preservation. However, overall survival does not appear to be improved, reflecting both effective surgical salvage after local recurrence and competing causes of death.     

Intensity-modulated radiation therapy for head and neck carcinoma

Intensity-modulated radiation therapy (IMRT) for head and neck tumors refers to a new approach that aims at increasing the radiation dose gradient between the target tissues and the surrounding normal tissues at risk, thus offering the prospect of increasing the locoregional control probability while decreasing the complication rate. As a prerequisite, IMRT requires a proper selection and delineation of target volumes. For the latter, recent data indicate the potential of functional imaging to complement anatomic imaging modalities. Nonrandomized clinical series in paranasal sinuses and pharyngolaryngeal carcinoma have shown that IMRT was able to achieve a very high rate of locoregional control with less morbidity, such as dry-eye syndrome, xerostomia, and swallowing dysfunction. The promising results of IMRT are likely to be achieved when many treatment conditions are met, for example, optimal selection and delineation of the target volumes and organs at risk, appropriate physical quality control of the irradiation, and accurate patient setup with the use of onboard imaging. Because of the complexity of the various tasks, it is thus likely that these conditions will only be met in institutions having large patient throughput and experience with IMRT. Therefore, patient referral to those institutions is recommended.     

A phase II study of concomitant hyperfractionated radiation therapy and double dose intra-arterial cisplatin for squamous cell carcinoma of the head and neck

This successor phase II study evaluates the tolerability and efficacy of concomitant hyperfractionated radiation therapy (HFX-RT) and double dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In doing so, this study represents further resurgence of the potential use of IA chemotherapy in the management of SCCHN. This has been enabled by the evolution of angiographic catheter/microcatherter technology. Between 1997 and 1999, 24 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8- 81.6 Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150mg/m2 given at the start of and during RT boost treatment [start of week 6 and 7]). Twenty-two patients (92%) had T4 disease and 14 (58%) N2/ N3 disease. Acute toxicity was limited to two grade 4 (8%) and 19 grade 3 (79%) mucosal events; and single grade 3 hematologic, infectious and skin events. Eight patients (33%) were unable to receive the second planned dose of IA cisplatin. Twenty-two patients had complete response (92%) at the primary site. Among 17 patients with positive neck disease 12 (71%) achieved complete response in the neck. Follow-up ranges from 7-30 months (median = 18 months) with 14 patients alive without disease, 2 alive with disease, 7 dead of disease and 1 dead of intercurrent disease. While concomitant HFX-RT and double dose IA cisplatin as used in this study is associated with encouraging response rates in this highly unfavorable subset of patients with locally advanced SCCHN it was not feasible. Future investigation of this novel treatment strategy utilizing modern angiographic catheter/microcatherter technology will involve a single dose of IA cisplatin with HFX-RT and dose intensification using neoadjuvant therapy.     

Six-week induction chemotherapy followed by concomitant chemoradiation therapy in stage IV head and neck cancer: a phase II study with organ-sparing purposes

The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by concomitant chemoradiotherapy and, when necessary, limited surgery. The study was a phase II non-randomized trial. Induction chemotherapy consisted of 6 weekly doses of carboplatin at AUC of 2 and docetaxel 30 mg/m(2) (1 h) followed by 5 cycles of docetaxel 25 mg/m(2)/day 1, 5-FU 600 mg/m(2) c.i. days 1-5, hydroxyurea 500 mg orally every 12 h for 11 and concomitant twice daily radiation therapy at 150 cGy/fraction given every other week per 5 cycles (TFHX), for a total radiation dose of 75 Gy. 13 cis-retinoic acid was administered for chemoprevention and systematic prophylaxis of mucositis with systemic amifostine and local GM-CSF was administered to all patients during TFHX. Conservative surgical resection was reserved to patients with no optimal response (PR > or =70%), whereas radical surgery was performed as salvage treatment. Thirteen patients (mean age 54.9 years, range 44-62; 12/13 site oropharynx, all stage IV) were enrolled: 31% of patients had ECOG performance status (PS) 0 and 69% had PS 1. Response to induction chemotherapy was analyzed in 12 patients: 2/12 (16.7%) achieved a partial response (PR) for an overall response (ORR) of 16.7%, 10/12 (83.3%) achieved stable disease (SD). TFHX was administered to 7 patients: 2 patients (28.6%) had complete remission (CR), 1 patient (14.3%) had PR for an ORR of 42.9%, 3 patients (42.8%) had SD and 1 patient (14.3%) had PD. At the completion of TFHX, 1 patient underwent local therapy. The toxicity was mild and consisted in: grade 3/4 neutropenia (7.7%), anemia (23.1%), diarrhea (15.4%), mucositis (7.7%), neurotoxicity (7.7%) during induction chemotherapy. During TFHX only 42.8% of grade 3/4 mucositis was observed. All patients spared organ/function. In conclusion, this regimen has been found feasible for its acceptable toxicity, particularly mucositis. However, the overall response rate and the data on survival were not satisfactory.     

Alternating gemcitabine and cisplatin with gemcitabine and radiation in stage IV squamous cell carcinoma of the head and neck.

BACKGROUND: In order to improve our cisplatin-5-fluorouracil (5-FU)-based alternating chemo-radiotherapy regimen, in 1996 we started an investigational program to explore a modified alternating regimen including gemcitabine given both with radiosensitizing and cytotoxic intent. MATERIALS AND METHODS: Based on our previous feasibility trial, we conducted a second study testing the feasibility and activity of the following schedule: gemcitabine 800 mg/m(2) on day 1 and cisplatin 20 mg/m(2) on days 2-5 (weeks 1, 4, 7 and 10) alternated with three courses of radiotherapy (RT) (weeks 2-3, 5-6 and 8-9) with conventional fractionation up to 60 Gy. Gemcitabine 300 mg/m(2) was also administered on the Monday of each week of RT. RESULTS: Forty-seven patients with stage IV (41 patients) unresectable squamous cell carcinoma of the head and neck (SCC-HN) or who had relapsed after surgery (6 patients) were enrolled. None had previously received chemotherapy or radiotherapy. Eight patients (18%) did not complete the treatment. Main grade 3-4 toxicities were as follows: neutropenia (44%); neutropenia with fever (12%); thrombocytopenia (37%); anemia (30% grade 3). One patient died in therapy due to sepsis. Most patients needed hospitalization and tube-feeding or parenteral nutrition. However, 44% of patients had a weight loss >10%. Thirty-four patients had a complete response (72%). Three partial responders were rendered disease-free by surgery (final complete response rate, 79%). At a median follow-up of 38 months actuarial 3-year overall survival, progression-free survival and loco-regional control are 43%, 39% and 64%, respectively. Data of locoregional control favorably compare with those from our database of patients treated with alternating cisplatin-fluorouracil and radiation within controlled clinical trials (64% versus 40%). CONCLUSIONS: The inclusion of gemcitabine into an alternating regimen seems to improve the results achievable with the original alternating program in stage IV patients. However, due to the high acute toxicity correlated, this intensive regimen should be managed by institutions well trained in multidisciplinary treatments.     

Final results of a phase II single-institutional trial with hyperfractionated radiation therapy (HFX) and four-weekly continuous cisplatin in locally advanced head and neck carcinoma

Background

To evaluate the efficacy and toxicity of hyperfractionated radiation therapy and continuous infusion of cisplatin on weeks 1 and 5 in locally advanced head and neck carcinoma.

Methods

There were 53 patients: 3 (5.7 %) T2 patients, 31 T3 patients (58.4 %), and 19 T4 patients (35.8 %). Forty-one patients (77.4 %) were N-positive. According to the AJCC, 40 (75.4 %) patients had stage IV and the rest stage III. Treatment consisted of hyperfractionated radiation therapy, 120 cGy bid to a dose of 76.8–81.6 Gy, and cisplatin 20 mg/m²/day administered by continuous infusion over 120 h during days 1–5 and 21–25 of radiation therapy.

Results

Tumor response and toxicity There were 40 (75.5 %) complete responses, 6 partial responses (11.3 %), and 5 (9.4 %) non-responses or progression. Two patients were non-evaluable for response due to toxic death. All patients had some acute toxicity grade, the most frequent being mucositis (grade 3–4 in 33 patients) and epithelitis (grade 3–4 in 30 patients). Regarding late toxicity, only 2/24 long-term survivors had tracheostomy, and none of them needed enteral nutrition. Survival and local control With a median follow-up of 66 months, the 5-year overall survival rate for all the series was 49.1 % (95 % CI 58.9–39.3 %) with a median survival duration of 32.83 months. Five-year local control was 68.4 % (95 % CI 81.3–55.5 %).

Conclusions

Hyperfractionated radiation therapy and continuous infusion of cisplatin during weeks 1 and 5 are an active treatment in patients with LAHNC. Nevertheless, new strategies are necessary to increase the local control rates and reduce the incidence of distant metastasis and second tumors.     

Carbon ion radiation therapy for prostate cancer: results of a prospective phase II study.

BACKGROUND AND PURPOSE: To determine the efficacy and feasibility of carbon ion radiotherapy (C-ion RT) for prostate cancer. PATIENTS AND METHODS: Between April 2000 and November 2003, 175 patients received C-ion RT using a recommended dose fractionation (66.0 GyE/20 fractions) established from prior studies. C-ion RT alone was performed for 33 patients constituting a low-risk group (Stage < or =T2a and PSA <20 ng/ml and Gleason score < or =6); the remaining 142 high-risk patients received an additional androgen deprivation therapy (ADT). RESULTS: The 4-year overall survival and bNED rates were 91% and 87%, respectively. Local control was achieved in all but one patient. The 4-year bNED rates were 87% in the low-risk group and 88% in the high-risk group. In very advanced diseases (Stage > or= T3a or PSA > or= 20 ng/ml or Gleason score > or =8), there was significant difference in the bNED rate according to period of ADT administration (ADT > or =24 months: 93%, ADT <24 months: 73%, p<0.01). Grade 2 late toxicities developed in 4 patients (2%) for the rectum and 9 patients (5%) for the genitourinary system but no Grade 3 or higher toxicity was observed. CONCLUSIONS: The effectiveness of C-ion RT for prostate cancer has been well confirmed. Based on these results, new study of a C-ion RT modified for the administration strategy of ADT according to the patient risk has been started by dividing patients into 3 groups, high-risk, intermediate-risk, and low-risk.     

Carboplatin and gemcitabine in the palliative treatment of stage IV non-small cell lung cancer: definitive results of a phase II trial

BACKGROUND: Cisplatin-containing regimens represent the gold standard in the treatment of advanced non-small cell lung cancer, but carboplatin is often preferred for its better toxic profile when palliation is the aim of the treatment. The synergistic effect and tolerability of carboplatin-gemcitabine combination are well known. In this phase II trial, we evaluated the activity and safety of a schedule with carboplatin and gemcitabine, defined in our previous phase I trial. METHODS: Thirty-seven patients with measurable stage IV non-small cell lung cancer were treated with carboplatin, AUC 4.5 mg/ml/min on day 1, and gemcitabine, 800 mg/m2 on days 1 and 8, every 21 days. All patients were treated until disease progression or intractable toxicity and were evaluated before each course of chemotherapy for toxicity and after every 3 courses for response. RESULTS: After a median follow-up of over 10 months, complete response, partial response, and stabilization of the disease were observed in 3 (8.1%), 9 (24.3%), and 15 patients (40.5%), respectively. Median time to progression was 7 months. At this writing, 27 patients have died, with a median survival of 10 months, and 29 (78.3%), 16 (43.2%), and 11 (29.7%) patients are alive after 6, 12, and 15 months of follow-up, respectively. Toxicity was mild, and mainly hematological, with a significant correlation with the number of courses of chemotherapy (P = 0.0003). CONCLUSIONS: Our results are comparable with those reported in the literature and confirm the good activity and tolerability of the carboplatin-gemcitabine combination. Up to 4 courses of chemotherapy with carboplatin and gemcitabine may represent an interesting option in the palliative treatment of non-small cell lung cancer.     

Combined therapy for stage III-IV head and neck cancer: preliminary results

As part of a combined modality treatment program using chemotherapy, surgery, and/or radiotherapy, 25 patients with previously untreated stage III or IV head and neck cancer received initial combination chemotherapy. Pathologically confirmed complete remission was noted in nine patients (36%). The overall objective major response rate (with all patients included in analysis) was 68%. The chemotherapy regimen included bleomycin, cisplatin, vinblastine, methotrexate, and 5-fluorouracil. A novel concept of drug scheduling was used, based on chemotherapy-induced improvement in RBC deformability. The underlying concept is that improved RBC deformability results in improved capillary blood flow and thereby, increased drug delivery to tumor cells. Treatment resulted in moderate hematologic and renal toxicity with no treatment-related deaths. This exceptionally high, pathologically confirmed complete response rate will hopefully provide a mechanism by which combined modality therapy can adequately be tested for its ability to prolong survival of patients with advanced head and neck cancer.     

Squamous cell carcinoma of the head and neck treated with radiation therapy: the impact of neck stage on local control

There have been several recent reports in the literature to indicate that the risk of failure at the primary site following radiation therapy is greater in patients with a clinically positive neck as opposed to those with a clinically negative neck at diagnosis. This is an analysis of 526 patients with squamous cell carcinoma of the head and neck who were treated with irradiation alone to the primary lesion with curative intent. All patients had follow-up for at least 2 years and were evaluable for analysis of local control. For each site and T stage, no evidence was found to indicate that the primary lesions were controlled less often in patients whose necks were clinically positive than in those whose necks were clinically negative.     

A phase II study of primary reirradiation in squamous cell carcinoma of head and neck.

BACKGROUND AND PURPOSE: In this prospective study, the effect of a second course of primary radiotherapy on locoregional control, survival and toxicity was investigated, in patients who underwent a second course of high dose irradiation for second primary or locoregional recurrent squamous cell head and neck carcinoma (HNSCC) in a previously irradiated area. PATIENTS AND METHODS: A total of 34 patients with second primary (n=26) or locoregional recurrent (n=8) tumours were treated with a second course of high dose radiotherapy. Patients were selected for re-irradiation in case of inoperable and/or unresectable tumours. In most cases, the target volume for re-irradiation was confined to the gross tumour volume (GTV). No elective radiotherapy was applied in the former high-dose area. A total dose of 46 Gy was applied to elective areas with a boost up to 60 Gy with conventional fractionation. The median follow-up period was 32 months. RESULTS: The locoregional control rate after 2 years was 27%. The 3-year overall survival was 22%. The most frequently reported acute side-effect was acute mucositis resulting in swallowing complaints. Pharyngeal and oesophageal late morbidity was also the most important late side-effect. In general, acute and late radiation-induced morbidity remained within acceptable limits. CONCLUSIONS: In conclusion, primary re-irradiation appears to be feasible in terms of acute and late radiation-induced toxicity. To improve outcome in terms locoregional control and survival, future studies should be focussed on optimising radiation schedules and the addition of concomitant chemotherapy.     

Supradose intra-arterial cisplatin and concurrent radiation therapy for the treatment of stage IV head and neck squamous cell carcinoma is feasible and efficacious in a multi-institutional setting: results of Radiation Therapy Oncology Group Trial 9615.

PURPOSE: To determine the feasibility of high-dose intra-arterial (IA) cisplatin and concurrent radiation therapy (RT) for head and neck squamous cell carcinoma in the multi-institutional setting (Multi-RADPLAT). PATIENTS AND METHODS: Eligibility included T4 squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Patients received cisplatin (150 mg/m(2) IA with sodium thiosulfate 9 g/m(2) intravenous [IV], followed by 12 g/m(2) IV over 6 hours, weekly for 4 weeks) and concurrent RT (70 Gy, 2.0 Gy/fraction, daily for 5 days over 7 weeks). Between May 1997 and December 1999, 67 patients from three experienced and eight inexperienced centers were enrolled, of whom 61 were eligible for analysis. RESULTS: Multi-RADPLAT was feasible (ie, three or four infusions of IA cisplatin and full dose of RT) in 53 patients (87%). The complete response (CR) rate was 85% at the primary site and 88% at nodal regions, and the overall CR rate was 80%. At a median follow-up of 3.9 years for alive patients (range, 0.9 to 6.1 years), the estimated 1-year and 2-year locoregional tumor control rates are 66% and 57%, respectively. The estimated 1-year and 2-year survival rates are 72% and 63%, respectively. The estimated 1-year and 2-year disease-free survival rates are 62% and 46%, respectively. The rates of grade 4 and 5 toxicities at the experienced and the inexperienced institutions were 14% and 0% v 47% and 4%, respectively. CONCLUSION: This intensive treatment regimen for head and neck cancer is feasible and effective in a multi-institutional setting.     

Surgery and postoperative radiation therapy in stage II endometrial carcinoma.

The traditional approach to patients with stage II endometrial carcinoma is preoperative radiation therapy (RT) followed by surgery. Currently, many patients are treated with primary surgery and postoperative RT. We retrospectively reviewed the outcome of 44 stage II (32 IIA, 12 IIB) patients who underwent surgery and postoperative RT. Nine (20%) had microscopic cervical involvement noted before surgery, and 35 (80%) had occult involvement noted postoperatively. Postoperative RT consisted of whole pelvic RT (WPRT) (50%), vaginal brachytherapy (VB) (18%), or both (32%). At a median follow-up of 40 months, the 5-year actuarial disease-free survival was 72.4%. Two patients (4%) had recurrence in the pelvis (one vagina, one lateral pelvis). Eighteen stage IIA patients treated with WPRT alone and eight stage IIA patients, without deep myometrial invasion (MI), were treated with VB alone, and remained controlled in the pelvis. Extrapelvic recurrences occurred in 12 patients (25%), primarily in those with deep MI and/or grade 2-3 disease. Our results suggest that patients with stage II endometrial carcinoma with microscopic or occult cervical involvement treated with surgery and postoperative RT have a favorable outcome. A high rate of pelvic control is achieved with RT tailored to the pathologic findings.     

Long-term treatment results of postoperative radiation therapy for advanced stage oropharyngeal carcinoma.

BACKGROUND. The authors report the long-term treatment results for advanced stage base of tongue (BOT) and tonsillar fossa (TF) carcinomas treated with surgery and postoperative radiation therapy (RT) at Memorial Sloan-Kettering Cancer Center. METHODS. Between 1973 and 1986, 51 patients with squamous cell carcinoma of the BOT (n = 31 patients) and TF (n = 20 patients) were treated with surgery plus RT. Indication(s) for RT included: advanced disease (Stage T3/T4, 34 patients [66%]); close or positive margins (33 patients, 64%) and multiple positive neck nodes (43 patients, 84%). RESULTS. The 7-year actuarial local control rates for BOT and TF lesions were 81% and 83%, respectively. Local control was achieved in 17 of 18 (94%) patients with T3 lesions, and 12 of 16 (75%) patients with T4 lesions. Among patients with positive or close margins who received postoperative doses of 60 Gy or more, the long-term control rate was 93%. The presence of a treatment interruption had a negative effect on the local control rates. The actuarial control among patients who required a treatment break was 64%; for those not requiring interruption of their treatment, the actuarial control was 93% (P = 0.05). At 7 years, the overall survival for all patients was 52%, and the disease-free survival was 64%. The actuarial incidence of neck failure was 21% and 18% for BOT and TF, respectively. The likelihood of having distant metastasis at 7 years for all patients was 30%. The actuarial incidence of having a second malignancy was 35% for patients with BOT disease. Second malignancy was not observed among patients with TF lesions. CONCLUSIONS. The authors conclude that surgery and postoperative RT can provide excellent long-term, disease-control rates for patients with advanced BOT and TF tumors. However, current strategies for BOT lesions have been directed at tongue preservation without surgery.     

A phase 2 study of bevacizumab with cisplatin plus intensity-modulated radiation therapy for stage III/IVB head and neck squamous cell cancer

BACKGROUND:

For patients with stage III through IVB head and neck squamous cell carcinoma (HNSCC), concurrent high‐dose cisplatin plus radiation therapy is a widely accepted standard of care. HNSCC tumors that express high levels of vascular endothelial growth factor have been associated with a worse prognosis, and bevacizumab may sensitize tumors to cisplatin and radiation.

METHODS:

Planned treatment consisted of definitive intensity‐modulated radiation therapy (IMRT) (total, 70 grays) with concurrent cisplatin (50 mg/m² on days 1, 2, 22, 23, 43, and 44) and bevacizumab (15 mg/kg on days 1, 22, and 43). The primary endpoint was 2‐year progression‐free survival (PFS), and overall survival (OS) was a secondary endpoint.

RESULTS:

Forty‐two previously untreated patients (34 men and 8 women; median age, 55 years; range, 27‐75 years) with stage III through IV HNSCC without distant metastasis (oropharyngeal carcinoma, 39 patients; laryngeal carcinoma, 3 patients) were treated. Human papillomavirus (HPV) status by was determined by in situ hybridization (HPV positive, 16 patients; HPV negative, 14 patients, unknown HPV status, 12 patients). The toxicities (determined according to version 3.0 of Common Terminology Criteria for Adverse Events Common) that were experienced by all patients (any grade) were mucositis, lymphopenia, leukopenia, throat pain, fatigue, and anemia. There were 2 treatment‐related deaths, including 1 sudden death and 1 death from aspiration pneumonia. The median follow‐up was approximately 31.8 months (range, <3 to 51 months). The 2‐year PFS rate was 75.9% (95% confidence interval, 63.9%‐90.1%), and the 2‐year OS rate was 88% (95% confidence interval, 78.6%‐98.4%). Among 32 patients for whom post‐treatment Head and Neck Performance Status Scores were obtained (median, 5.6 months after completing radiation therapy), scores of 100 for eating, speech, and diet, respectively, were recorded among 75%, 84%, and 50% of patients.

BACKGROUND:

The addition of bevacizumab to high‐dose cisplatin plus IMRT did not appear to increase toxicity to unacceptable levels among patients with HNSCC, and the efficacy results were encouraging. Cancer 2012. © 2012 American Cancer Society.     

Organ-sparing radiation therapy for head and neck cancer

To improve locoregional tumor control and survival in patients with locally advanced head and neck cancer (HNC), therapy is intensified using altered fractionation radiation therapy or concomitant chemotherapy. However, intensification of therapy has been associated with increased acute and late toxic effects. The application of advanced radiation techniques, such as 3D conformal radiation therapy and intensity-modulated radiation therapy, is expected to improve the therapeutic index of radiation therapy for HNC by limiting the dose to critical organs and possibly increasing locoregional tumor control. To date, Review articles have covered the prevention and treatment of radiation-induced xerostomia and dysphagia, but few articles have discussed the prevention of hearing loss, brain necrosis, cranial nerve palsy and osteoradionecrosis of the mandible, which are all potential complications of radiation therapy for HNC. This Review describes the efforts to prevent therapy-related complications by presenting the state of the art evidence regarding advanced radiation therapy technology as an organ-sparing approach.