Gideon Marshak

Prognostic factors for local control of early glottic cancer : The Rabin Medical Center retrospective study on 207 patients

PURPOSE Different radiation therapy schedules and devices have been used over the last 20 years at Rabin Medical Center in patients with early glottic cancer. The aim of the present retrospective analysis was to identify the subgroup of patients at high risk of failure of radiation treatment. MATERIALS AND METHODS Between 1974 and 1994, 207 patients with squamous cell carcinoma of the glottis, 182 Stage T1 and 25 Stage T2, underwent definitive radiation therapy. During this period, treatment was administered with different radiation devices (60Co or 6-MV X ray), using different dose/fraction protocols (1.8 or 2 Gy per day, 5 or 6 fractions per week), total doses (42-77.4 Gy), overall radiation times, and delays. These treatment variables, in addition to certain patient and tumor characteristics, were correlated with local control at a median follow-up of 57 months (range 18-265 months). RESULTS The 5-year local control rates for T1 and T2 tumors were 88% and 73%, respectively. Univariate analysis showed that smoking, diabetes mellitus, anterior commissure involvement, T stage, and extension of tumor to one third or more of the vocal cord were highly significantly correlated with decreased local control. None of the treatment variables, including dosage at which complete tumor regression was noted, were found to be predictive. By multivariate analysis, only anterior commissure involvement was found to be highly significant (risk ratio 1.9, 95% CI 1.2-3.0, p = 0.027), and T stage was borderline significant (risk ratio 1.6, 95% CI 1.0-2.5, p = 0.054). CONCLUSION This study suggests that only two tumor characteristics are predictive of local failure of early glottic cancer: anterior commissure involvement and T stage. Treatment variables apparently do not influence local control.

MicroRNAs as a potential prognostic factor in gastric cancer

AIM To compare the microRNA (miR) profiles in the primary tumor of patients with recurrent and non-recurrent gastric cancer. METHODS The study group included 45 patients who underwent curative gastrectomies from 1995 to 2005 without adjuvant or neoadjuvant therapy and for whom adequate tumor content was available. Total RNA was extracted from formalin-fixed paraffin-embedded tumor samples, preserving the small RNA fraction. Initial profiling using miR microarrays was performed to identify potential biomarkers of recurrence after resection. The expression of the differential miRs was later verified by quantitative real-time polymerase chain reaction (qRT-PCR). Findings were compared between patients who had a recurrence within 36 mo of surgery (bad-prognosis group, n = 14, 31%) and those who did not (good-prognosis group, n = 31, 69%). RESULTS Three miRs, miR-451, miR-199a-3p and miR-195 were found to be differentially expressed in tumors from patients with good prognosis vs patients with bad prognosis (P < 0.0002, 0.0027 and 0.0046 respectively). High expression of each miR was associated with poorer prognosis for both recurrence and survival. Using miR-451, the positive predictive value for non-recurrence was 100% (13/13). The expression of the differential miRs was verified by qRT-PCR, showing high correlation to the microarray data and similar separation into prognosis groups. CONCLUSION This study identified three miRs, miR-451, miR-199a-3p and miR-195 to be predictive of recurrence of gastric cancer. Of these, miR-451 had the strongest prognostic impact.

Squamous cell carcinoma of the oral tongue in young patients.

Objectives/Hypothesis: Cancer of the tongue is reported with increasing frequency in young people. The objective of this work was to study the biologic and clinical course of the disease in this group. The clinical course of the disease in this patient group remains controversial.

Basaloid squamous carcinoma of the larynx

BACKGROUND Basaloid squamous cell carcinoma (BSCC) is a distinct variant of squamous cell carcinoma that was first described by Wain et al in 1986. Since then, about 160 cases have been reported in the literature. Only 40 cases have been described in the larynx. METHODS Four cases of BSCC of the larynx treated in our department between 1986 and 2000 are presented. The clinical features, biological behavior, and histopathological and immunohistochemical characteristics of this uncommon tumor are described, and the relevant literature is reviewed. RESULTS The main clinical presentation did not differ from other histological types of laryngeal carcinoma. The clinical course, however, was much more aggressive. All the patients received aggressive therapy including radical surgery and radiation. Two patients received chemotherapy. Two of the 4 patients presented died of distant metastasis shortly after diagnosis and treatment. CONCLUSIONS The finding of this study with a limited number of patients supports previous reports suggesting that BSCC is a highly aggressive tumor that presents in older population with male predominance. The frequency of associated regional as well as distant metastases suggests that aggressive treatment is indicated and that systemic chemotherapy should be contemplated.

Invasive well-differentiated thyroid carcinoma: effect of treatment modalities on outcome.

OBJECTIVE: Well-differentiated thyroid carcinoma is considered an indolent malignant disease. Although rare, extrathyroidal invasion is associated with a worse prognosis and increased risk of morbidity. Management remains controversial, with some authors advocating conservative treatment with preservation of midline structures and others, aggressive extensive en bloc resection. The aim of this study was to report our 40-year experience with invasive thyroid carcinoma, with emphasis on the clinical characteristics and the effect of different treatment modalities on survival. STUDY DESIGN AND SETTING: A retrospective study including a file review of 1,200 patients with a diagnosis of well-differentiated thyroid carcinoma of whom 49 (5%) showed involvement of an adjacent structure (larynx, trachea and esophagus) (study group). Type of surgery, radiation treatment, radioiodine treatment, and patient demographics were evaluated. RESULTS: Compared to the rest of the patients, the study group was characterized by a higher rate of male patients (39% vs 25%), and older average age (58 vs 45 years). Average size of the primary tumor was 3.7 cm. Sixteen patients underwent radical surgery and 33 conservative surgery followed by radio-iodine treatment. Five-year survival and recurrence rates for the whole group were 78% and 52%, respectively. The only statistically significant factor for survival was large tumor size. Distant metastases developed in 46% of patients, all in the lungs. Ten of 14 deaths were due to distant metastases. External radiation, used in 52% of the patients, was associated with worse prognosis. CONCLUSION: Conservative procedures followed by radioiodine treatment are associated with similar survival rates as aggressive techniques, with less perioperative mortality and lower overall morbidity. SIGNIFICANCE: This study provides further evidence that in cases of invasive thyroid tumors the extent of the primary surgery seems to have no influence on survival. EBM rating: C-4

Vocal cord palsy: possible late complication of radiotherapy for head and neck cancer.

Cranial nerve palsies are uncommon complications of radiotherapy for head and neck cancer. A review of the literature reveals that cranial nerve damage after radiotherapy has been reported for the optic, oculomotor, trigeminal, abducens, cochlear, vagus, spinal accessory, and hypoglossal nerves. The hypoglossal nerve appears to be the most commonly affected, and the recurrent laryngeal nerve is seldom involved. The case histories of three patients who developed vocal cord palsy from 21 to 34 years after a course of curative or postoperative radiotherapy for carcinoma of the head and neck are presented. Two patients had bilateral palsy, and in the third patient, bilateral damage cannot be excluded. Physical examination and radiographic investigations on admission and on follow-up did not demonstrate any evidence of tumor recurrence, cervical or distant metastases, or second primary tumors. The distinction between irradiation-induced palsy and that due to malignancies is emphasized.

Growth retardation and destruction of experimental squamous cell carcinoma by interstitial radioactive wires releasing diffusing alpha-emitting atoms.

In the present study, we examined the antitumoral effects caused by the release of alpha emitting radioisotopes into solid squamous cell carcinoma (SCC) tumors. Using a novel method termed DART (Diffusing Alpha‐emitters Radiation Therapy), we assessed the efficacy of short‐lived daughters of 224Ra releasing alpha particles, dispersing in the malignant tissue, to cause tumor growth retardation and destruction. It was carried out using specially designed wires loaded with 224Ra activities in the range of 7–42 kBq in a set of experiments performed on BALB/c and nude mice bearing metastatic SCC tumors derived from either mouse SQ2 or human CAL27 cell lines. The insertion of a DART wire to the center of 6–7 mm primary tumors, retarded tumor growth, reduced lung metastatic load, prolonged life expectancy and in some cases caused tumor eradication. These effects were enhanced either when treating smaller tumors or treating identical tumors with 2 DART wires. Similar experiments on human‐derived SCC tumors in nude mice were consistent with the outcomes of the murine model. Histological assessments revealed the tissue damage pattern, and indicated a role for the tumor vasculature in the dispersion of the atoms and the propagation of the damage. Our findings indicate that Diffusing Alpha‐emitting Radiation Therapy is effective in a model system using SCC primary tumors. The in situ destruction of primary solid tumors by DART is evidently a necessary step toward curing cancer and might be augmented by chemotherapy and other modalities such as immunotherapy or antigrowth factors agents.

Malignant melanomas of female urethra

Primary melanoma of the female urethra is extremely rare. Treatment by surgery, radiation, and chemotherapy has been uniformly ineffective. We herein report on 2 patients with primary malignant melanoma of the urethra treated with immunotherapy and chemotherapy. The first patient died four years after the initial diagnosis, and the second died after two years. Chemo-immunotherapy may be considered as an additional, palliative form of treatment in the management of primary melanoma of the female urethra, but cystourethrectomy should be the initial form of treatment.

Interstitial wires releasing diffusing alpha emitters combined with chemotherapy improved local tumor control and survival in squamous cell carcinoma-bearing mice.

The objective of this study was to examine the combined effect of diffusing alpha‐emitter radiation therapy (DART) together with the chemotherapeutic agent cisplatin on tumor development.

Laryngeal carcinoma in females

Between 1950 and 1992, 96 women with squamous cell carcinoma of the larynx were diagnosed and treated in the Department of Otolaryngology and Oncology at Beilinson Medical Center, Israel, and Long Island College Hospital, Brooklyn, New York. Fifty-seven female patients (59%) had glottic carcinoma, 72% of them in stage I. Thirty-eight had supraglottic carcinoma, 68% of them in stages II and III. One patient had stage I subglottic carcinoma. Treatment varied between radiotherapy, surgery, or combined surgery with radiation and/or chemotherapy. The 5-year survival rate was 87%. Although most of the patients had glottic carcinoma in stage I, there was also a high percentage with supraglottic carcinoma, most in advanced stages and with metastases to other regions. The prognosis is not different from that in men. Smoking is an important factor in glottic carcinoma, but not as important as in males.