BACKGROUND We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant highdose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

/pdf/radiotherapy-plus-cetuximab-for-squamous-cell-carcinoma-of-f0pcqo8jys.pdf

Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck

The importance of knowledge on tolerance of normal tissue organs to irradiation by radiation oncologists cannot be overemphasized. Unfortunately, current knowledge is less than adequate. With the increasing use of 3-D treatment planning and dose delivery, this issue, particularly volumetric information, will become even more critical. As a part of the NCI contract N01 CM-47316, a task force, chaired by the primary author, was formed and an extensive literature search was carried out to address this issue. In this issue. In this manuscript we present the updated information on tolerance of normal tissues of concern in the protocols of this contract, based on available data, with a special emphasis on partial volume effects. Due to a lack of precise and comprehensive data base, opinions and experience of the clinicians from four universities involved in the contract have also been contributory. Obviously, this is not and cannot be a comprehensive work, which is beyond the scope of this contract.

Tolerance of normal tissue to therapeutic irradiation.

Head and neck cancer.

Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumour spread and surgical excision.

Context.—For the treatment of a single metastasis to the brain, surgical resection
combined with postoperative radiotherapy is more effective than treatment
with radiotherapy alone. However, the efficacy of postoperative radiotherapy
after complete surgical resection has not been established.Objective.—To determine if postoperative radiotherapy resulted in improved neurologic
control of disease and increased survival.Design.—Multicenter, randomized, parallel group trial.Setting.—University-affiliated cancer treatment facilities.Patients.—Ninety-five patients who had single metastases to the brain that were
treated with complete surgical resections (as verified by postoperative magnetic
resonance imaging) between September 1989 and November 1997 were entered into
the study.Interventions.—Patients were randomly assigned to treatment with postoperative whole-brain
radiotherapy (radiotherapy group, 49 patients) or no further treatment (observation
group, 46 patients) for the brain metastasis, with median follow-up of 48
weeks and 43 weeks, respectively.Main Outcome Measures.—The primary end point was recurrence of tumor in the brain; secondary
end points were length of survival, cause of death, and preservation of ability
to function independently.Results.—Recurrence of tumor anywhere in the brain was less frequent in the radiotherapy
group than in the observation group (9 [18%] of 49 vs 32 [70%] of 46; P<.001). Postoperative radiotherapy prevented brain
recurrence at the site of the original metastasis (5 [10%] of 49 vs 21 [46%]
of 46; P<.001) and at other sites in the brain
(7 [14%] of 49 vs 17 [37%] of 46; P <.01). Patients
in the radiotherapy group were less likely to die of neurologic causes than
patients in the observation group (6 [14%] of 43 who died vs 17 [44%] of 39; P =.003). There was no significant difference between the
2 groups in overall length of survival or the length of time that patients
remained functionally independent.Conclusions.—Patients with cancer and single metastases to the brain who receive
treatment with surgical resection and postoperative radiotherapy have fewer
recurrences of cancer in the brain and are less likely to die of neurologic
causes than similar patients treated with surgical resection alone.

https://jamanetwork.com/journals/jama/articlepdf/188127/joc80445.pdf

Postoperative radiotherapy in the treatment of single metastases to the brain: a randomized trial.

Revised and updated, this edition provides a comprehensive, authoritative approach to head and neck cancer. Page after page is packed with clear and instructive illustrations - line drawings and halftones; fibre optic and microscopic examinations; CT scans; "before and after treatment" figures; plus many full-colour illustrations.

Management of Head and Neck Cancer: A Multidisciplinary Approach

BACKGROUND
The treatment of patients with squamous cell carcinoma (SCC) of the oropharynx remains controversial. No randomized trial has addressed adequately the question of whether surgery (S), radiation therapy (RT), or combined treatment is most effective.

METHODS
Treatment results from North American academic institutions that used S with or without adjuvant RT (S ± RT) or used RT alone or followed by neck dissection (RT ± ND) for patients with SCC of the tonsillar region or the base of tongue were compiled through a MEDLINE search (from 1970 to August, 2000) and from the references cited in each report. Studies were eligible for inclusion if they contained direct, actuarial (life-table), or Kaplan–Meier calculations for the following end points: local control, local-regional control, 5-year absolute survival, 5-year cause specific survival, or severe or fatal treatment complications. Weighted average results, which took into account series size, were calculated for each end point for the purposes of treatment comparison. Results and conclusions were based on data from 51 reported series, representing the treatment of approximately 6400 patients from the United States and Canada.

RESULTS
The results for patients with SCC of the base of tongue who underwent S ± RT versus RT ± ND, respectively, were as follows: local control, 79% versus 76% (P = 0.087); local-regional control, 60% versus 69% (P = 0.009); 5-year survival, 49% versus 52% (P = 0.2); 5-year cause specific survival, 62% versus 63% (P = 0.4); severe complications, 32% versus 3.8% (P < 0.001); and fatal complications, 3.5% versus 0.4% (P < 0.001). The results for patients with SCC in the tonsillar region who underwent S ± RT versus RT ± ND, respectively, were as follows: local control, 70% versus 68% (P = 0.2); local-regional control, 65% versus 69% (P = 0.1); 5-year survival, 47% versus 43% (P = 0.2); 5-year cause specific survival, 57% versus 59% (P = 0.3); severe complications, 23% versus 6% (P < 0.001); and fatal complications, 3.2% versus 0.8% (P < 0.001).

CONCLUSIONS
The information in this article provides a useful benchmark for evidence-based counseling of patients with SCC of the oropharynx. The rates of local control, local-regional control, 5-year survival, and 5-year cause specific survival were similar for patients who underwent S ± RT or RT ± ND, whereas the rates of severe or fatal complications were significantly greater for the S ± RT group. Furthermore, available data on the functional consequences of treatment suggest the superiority of RT ± ND. The authors conclude that RT ± ND is preferable for the majority of patients with SCC of the oropharynx. Cancer 2002;94:2967–80. © 2002 American Cancer Society.

DOI 10.1002/cncr.10567

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.1002/cncr.10567

Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both.

Two hundred and eighty patients with previously untreated large bowel adenocarcinoma were retrospectively evaluated following complete primary resection to determine patterns of recurrence. One hundred and five patients (37%) subsequently developed recurrent disease. Sixty percent (63/105) presented with local recurrence alone, 14% (15/105) with concomitant local recurrence and distant metastases, and 26% (27/105) with distant metastases alone. Ninety-two percent of local recurrences developed in structures contiguous to the operative area of the incision. The degree of tumor anaplasia and depth of tumor penetration into the bowel wall influenced the rate of local recurrence. Through 5 years, local recurrence without clinical evidence of distant metastases was the most common cause of death. Plans for adjuvant radiation therapy are discussed.

Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum

Purpose: To investigate the risk of radiation-induced optic neuropathy according to total radiotherapy dose and fraction size, based on both retrospective and prospectively collected data.

Methods and Mateirials: Between October 1964 and May 1989, 215 optic nerves in 131 patients received fractionated external-beam irradiation during the treatment of primary extracranial head and neck tumors. All patients had a minimum of 3 years of ophthalmologic follow-up (range, 3 to 21 years). The clinical end point was visual acuity of 20100 or worse as a result of optic nerve injury.

Results: Anterior ischemic optic neuropathy developed in five nerves (at mean and median times of 32 and 30 months, respectively, and a range of 2–4 years). Retrobulbar optic neuropathy developed in 12 nerves (at mean and median times of 47 and 28 months, respectively, and a range of 1–14 years). No injuries were observed in 106 optic nerves that received a total dose of < 59 Gy. Among nerves that received doses of ≥ 60 Gy, the dose per fraction was more important than the total dose in producing optic neuropathy. The 15-year actuarial risk of optic neuropathy after doses of ≥ 60 Gy was 11% when treatment was administered in fraction sizes of < 1.9 Gy, compared with 47%, when given in fraction sizes of ≥ 1.9 Gy. The data also suggest an increased risk of optic nerve injury with increasing age.

Conclusion: As there is no effective treatment of radiation-induced optic neuropathy, efforts should be directed at its prevention by minimizing the total dose, paying attention to the dose per fraction to the nerve, and using reduced-field techniques where appropriate to limit the volume of tissues that receive high-dose irradiation.

Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors

Total surgical excision is the main goal of therapy for intracranial meningiomas. The controversy today involves the efficacy of postoperative radiation therapy. To evaluate this question, 132 patients with benign intracranial meningiomas, treated between October 1964 and April 1985, were evaluated. All patients had a minimum 2-year follow-up. The actuarial local control rates at 10 years for the three treatment groups were as follows: subtotal excision alone, 18%; subtotal excision plus postoperative radiation therapy, 82%; and total excision alone, 77%. The actuarial determinate survival rates at 10 years were 49%, 81%, and 93%, respectively. Postoperative radiation therapy was also effective for patients treated at the time of the first recurrence, with an actuarial local control rate at 10 years after salvage treatment of 30% for patients treated with surgery alone and 89% for patients receiving postoperative radiation therapy at the time of salvage. This analysis suggests that radiation therapy has a significant role in the treatment of subtotally excised and recurrent intracranial meningiomas.

Rodney R. Million

Papers

Management of Head and Neck Cancer: A Multidisciplinary Approach

Squamous cell carcinoma of the oropharynx: surgery, radiation therapy, or both.

Patterns of recurrence following surgery alone for adenocarcinoma of the colon and rectum

Radiation optic neuropathy after megavoltage external-beam irradiation: analysis of time-dose factors

The meningioma controversy: postoperative radiation therapy.