J.F. McIntyre

Neuroendocrine tumors of the sinonasal tract. Results of a prospective study incorporating chemotherapy, surgery, and combined proton-photon radiotherapy.

The authors report the results of a prospective study of patients with malignant neuroendocrine tumors of the sinonasal tract who received multimodality treatment incorporating high‐dose proton‐photon radiotherapy.

Re-irradiation of laryngeal carcinoma—Techniques and results

PURPOSE Occasionally in the long-term survivors of early carcinoma of the larynx, following radiation therapy a second carcinoma may arise from the previously irradiated larynx. Traditionally, management of such lesions is by non-radiation means in the belief that a further full course of radiation therapy is not possible and may exceed the tolerance of the normal laryngeal structures. Unfortunately, surgical treatment of the second carcinoma is often either total or partial laryngectomy which may not be acceptable to the patients and therefore radiation therapy is used as an alternative. METHODS AND MATERIALS This paper presents our experience in re-irradiation of laryngeal carcinomas arising from the previously irradiated larynx. As of October 1992 a total of 20 patients were available for evaluation. Most patients had Stage I and II laryngeal carcinoma and received high doses of re-irradiation ranging from 60 to 70 Gy either by conventional or accelerated hyperfractionation schemes. RESULTS The 5-year actuarial local control and survival rates were 60 to 93%, respectively. The majority of the survivors had relatively normal and functional larynges. Those who failed locally had total laryngectomy without significant postoperative complications. CONCLUSION With this information the radiation tolerance of laryngeal structures is found to be much higher than commonly believed and re-irradiation for early carcinoma of the larynx is possible and proved to be a useful alternative to surgery and laryngectomy is therefore reserved for failure. The techniques of re-irradiation will be discussed.

Germline mutations of the p53 tumor suppressor gene in children with osteosarcoma

PURPOSE We investigated the possibility that a significant proportion of children with osteosarcoma harbor germline mutations of the p53 tumor suppressor gene and, therefore, this subgroup of pediatric cancer patients should be considered for large-scale predictive testing. PATIENTS AND METHODS Genomic DNA extracted from peripheral-blood leukocytes from 235 unselected children with osteosarcoma from 33 institutions were screened for the presence of germline p53 mutations using constant denaturant gel electrophoresis (CDGE). Exons 5 through 8 were evaluated in all patients and exon 2 and exon 9 were analyzed in 59 and 95 patients, respectively. Those samples that showed aberrant migration on CDGE were sequenced or analyzed by restriction enzyme digestion of polymerase chain reaction (PCR) products to confirm the nature of the gene alteration. RESULTS In 18 samples, CDGE showed fragments of the p53 gene with altered electrophoretic mobilities compared with wild-type p53. DNA sequencing showed that 11 samples had an identical, previously described polymorphism. The other seven contained heterozygous p53 mutations located in exon 5 (n = 3), exon 6 (n = 1), exon 7 (n = 1), and exon 8 (n = 2). Six alterations were missense mutations and one was a nonsense mutation. Three of these patients had first-degree relatives with cancer. One of these three kindreds had a family history consistent with Li-Fraumeni syndrome (LFS). CONCLUSION We identified germline p53 mutations in seven of 235 (3.0%) children with osteosarcoma. Four of these mutations were found in patients who did not have first-degree relatives with cancer. Although genetic transmission of the altered p53 gene could not be tested in this survey because of how it was designed, it is possible that predictive testing for p53 mutations could identify unaffected relatives of gene carriers who also have a high risk for the development of cancer. This study provides evidence for the importance of considering children with osteosarcoma for predictive testing for germline p53 mutations.

Acute ocular toxicity and long-term visual outcome of primary and adjuvant hyperfractionated/accelerated radiation therapy of advanced paranasal sinus cancer employing proton irradiation

Materials/Methods: Between 1991 and 2001, HART (4 MeV photons and 160 MeV protons) was used to treat 35 pts with advanced stage primary (n 32) or recurrent (n 3) malignant tumors of the paranasal sinuses for whom full neuroophtalmologic follow-up was obtained. Median age was 52 years (range, 18.5-74.4). Ten (29%) unresectable patients were treated with primary and 25 (71%) with adjuvant radiation therapy, respectively. Chemotherapy (CT) was administered to 13 (37%) patients, however, none received concurrent CT. Prospectively specified neuro-ophtalmologic follow-up consisted of pupillary examination, exophtalmometry, color vision and ocular pressure measurements, motility testing, as well as dilated fundus exam and Goldmann visual field. The median dose to the macroscopic gross tumor volume (GTV) was 69.6 CGE (range, 60-76.6 CGE, CGE proton Gy 1.1 RBE). Optical apparatus dose constraint was 2 CGE/day and 56 CGE total dose, respectively. If clinically indicated, the treating physician had the option to relax the optical dose constraints. Median GTV and clinical tumor volume were 90 cc (range, 5.4-318) and 251 cc (range, 40.9-636), respectively. Lens and retinal late complications were graded according to objective portion of the SOMA scale of the Late Effects of Normal Tissue (LENT) Scoring system. Other late ocular/visual symptoms were classified according to the NCI Common Toxicity Criteria (CTC) grading system. Disease-free Survival (DFS) and visual complication free survival (CFS) rate were calculated using KaplanMeier method. The studied risk factors for late visual complications included dose, gender, age, acute ocular toxicity, GTV volume, adjuvant chemotherapy and follow-up length. Statistical analysis was performed on SAS 8.1 software, using adequate methods including Student T-test and Log rank analysis. The median follow-up was 37.6 months (range, 4.4-122.8).