Israel Medical Association Journal

Background: Anal squamous cell carcinoma (ASqCC) is a rare malignancy, traditionally treated with combined chemoradiation, with a continuous infusion of 5-fluorouracil (5-FU) and mitomycin C (MMC). Replacing intravenous (IV) 5-FU with oral capecitabine (oral fluoropyrimidine) has been reported as a non-inferior treatment option. However, these data are scarce, with variable results.

Objectives: To examine the outcome of patients with ASqCC treated with either IV 5-FU or capecitabine concomitantly with radiation therapy. To compare treatment side effects, local recurrence, and general outcome.

Methods: We reviewed charts of patients who were diagnosed with stage I–III ASqCC. All participating patients received chemoradiation at the Assuta Medical Center between 2011 and 2019.

Results: In this study, 43 patients with ASqCC were eligible; 14 received 5-FU and 29 were treated with capecitabine. Basic characteristics were similar between the two groups, with longer follow-up for the 5-FU group. Six months following treatment, 100% (13/13 with adequate follow-up) of the 5-FU group had complete clinical response, compared to 84% in the capecitabine group (21/24), P = 0.143. The local recurrence incidence was higher in the 5-FU group at 23% (7, 10, 26 months following therapy, and none in the capecitabine group (P = 0.088). Although local and hematological toxicities were similar between groups, one patient receiving capecitabine died during chemoradiotherapy.

Conclusions: Oral capecitabine demonstrated non-inferior disease control in ASqCC treated with chemoradiotherapy. We recommend oral capecitabine over continuous IV 5-FU in locally and locally advanced ASqCC. Close monitoring of side effects is required to reduce major toxicity.

Background: Recent studies show a high risk of developing malignancy in patients with Fanconi anemia. The most common solid tumor in this condition is head and neck squamous cell carcinoma (HNSCC) and there is often uncertainty and about disease behavior as well as chemotherapy and radiation response.

Objectives: To describe and characterize HNSCC among Fanconi anemia patients on the Israeli Fanconi Registry

Methods: Our study population included patients in Israel's inherited bone marrow failure registry who were diagnosed with Fanconi anemia between1980 and 2016. Demographic, clinical, and laboratory data were collected from patient charts.

Results: From the collected data, HNSCC was confirmed in 6/111 (5.4%) Fanconi anemia patients; 1 (17%) had classic HNSCC risk factors of tobacco abuse and 4 (56%) had undergone primary surgery. The 3 (50%) receiving concurrent chemoradiotherapy had mild side effects, while half developed metachronous primary malignancy, and all developed > 2 primary malignancies. The overall median survival of the patients in our study was 14 (0.5–57) months.

Conclusions: Fanconi anemia patients have a very high risk of developing HNSCC. Proactive screening for malignancies is needed for the head and neck regions. We also found that chemoradiotherapy can be used safely in high-stage cancers.

Background: Leukoplakia of the vocal cords may represent a pre-cancerous lesion of the larynx. The management of cases of recurrent leukoplakia with pathologically proven dysplasia is still controversial.

Objectives: To present a series of patients with recurrent vocal cord leukoplakia and to examine their malignant transformation rate in relation to the clinical characteristics, risk factors, and histological findings.

Methods: A retrospective cohort study was conducted between 1999 and 2017. The study comprised 52 patients with recurrent leukoplakia of the vocal cords who required ≥ 2 direct laryngeal procedures within a minimum of 3 months between each procedure. Malignant transformation rate over follow-up period, risk factors for malignant transformation, and interval to develop laryngeal squamous cell carcinoma were investigated.

Results: All patients presented with hoarseness. An average of three procedures per patient was performed (range 2–13). Ten male patients (19.2%) developed squamous cell carcinoma. Of these, four with severe dysplasia developed SCC within 19 months of the first direct laryngoscopy. In the six other patients, SCC developed within an average of 3.7 years. The follow-up period ranged from 9–253 months (mean 109 months). Heavy smoking and severe dysplasia in the first biopsy were found to be significant risk factors for developing squamous cell carcinoma, as was male gender.

Conclusions: We showed an increased malignant transformation rate in recurrent leukoplakia cases among heavy smokers and male patients. In addition, severe dysplasia at initial diagnosis was a risk factor for SCC development. Close follow-up of patients with recurrent leukoplakia is warranted.

Background: Several types of human papillomavirus (HPV) have been found to be associated with oral squamous cell carcinoma (OSCC). Still, the significance of HPV infection and its relationship to patient prognosis remains an important matter of debate.

Objectives: To investigate the incidence of HPV infection in OSCC patients in northern Israel populations to determine its role in the etiology and prognosis of OSCC.

Methods: OSCC tissues were gathered from the pathology departments at Rambam and Padeh medical centers in northern Israel. HPV DNA typing and immunohistochemistry for p16INK4A antibodies were conducted to evaluate their incidence in OSCC tissues. Statistical analysis regarding its expression in the different sub-populations (Jews, Arabs, Druze) was conducted using chi-square and Fisher’s exact tests.

Results: The study included 82 patients: 53 men and 29 woman; median age 62.1 years; 54 Jews, 25 Arabs, and 3 Druze. The overall incidence of HPV expression was 45% (n=37). The median age of HPV-positive patients was 53 years vs. 65.8 in the negative group (P < 0.001). The 5 year overall survival of HPV-positive patients was not significantly higher than HPV-negative patients. A significant association was found between P16 expression and overall survival (log-rank P = 0.001).

Conclusions: HPV infection in OSCC was not found to be significant in this study; however, P16 expression in the tumor tissue was found to be a positive prognostic factor for better survival.

Background: Clinicopathological risk factors for cutaneous squamous cell carcinoma of the head and neck (CSCCHN) are associated with local recurrence and metastasis. 

Objectives: To compare the incidence and risk factors of CSCCHN by age and gender in order to help refine the clinical evaluation and treatment process.

Methods: Clinical and pathological data of all patients diagnosed with CSCCHN during 2009–2011 were obtained from a central pathology laboratory in Israel. Estimated incidence rate calculation was standardized to the 2010 Israeli population. Independent risk factors for poorly differentiated CSCCHN were analyzed using logistic regression.

Results: CSCCHN was diagnosed in 621 patients. Mean age was 75.2 years; mean tumor horizontal diameter was 11.1 ± 6.8 mm. The overall estimated incidence rate in males was higher than in females (106.2 vs. 54.3 per 1,000,000, P < 0.001). Twenty cases (3.2%) had poorly differentiated CSCCHN. Scalp and ear anatomic locations were observed more often in males than in females (22.1% vs. 6.1% and 20.3% vs. 3.3%, respectively, P < 0.001). Per 1 mm increment, tumor horizontal diameter increased the risk for poorly differentiated CSCCHN by 6.7% (95%CI 1.3–12.4%, P = 0.014). 

Conclusions: CSCCHN clinicopathological risk factors are not distributed evenly among different age and gender groups. 

 

Objectives: To evaluate the feasibility of induction chemotherapy with docetaxel-cisplatin-5-flurouracil (TPF) followed by external beam radiotherapy (EBRT) with concomitant chemotherapy (CRT) or cetuximab (ERT) in the treatment of patients with advanced SCCHN.

Methods: We reviewed the data of all patients with advanced SCCHN, stage III and IV, treated in 2007–2010. Tolerability was assessed and scored according to the proportion of patients completing the planned study protocol. Toxicity was scored using the U.S. National Cancer Institute Common Toxicity Criteria (version 4) for classification of adverse events.

Results: The study included 53 patients. TPF was initiated at a reduced dose in 13 patients (25%). Twenty-two patients (41.5%) received primary prophylaxis with granulocyte colony-stimulating factor (GCSF) and 42 (77%) completed treatment according to schedule. During the induction phase one patient (2%) died and 24 (45%) had one or more grade 3-4 complications. The number of patients who developed neutropenia was lower in the group that received primary GCSF prophylaxis. Secondary dose reductions were required in 21% of the patients.

Conclusions: Induction TPF was associated with grade 3-4 toxicity. Prophylaxis with GCSF should be part of the treatment regimen.

The incidence of invasive uterine cervical cancer in Israeli Jewish women is persistently lower than in many other countries, although the frequency of premalignant lesions is similar to that in other populations. Most characteristics, except certain traditional habits, are similar to those in other populations. The incidence among women born in North Africa and their Israeli born descendants is significantly higher than in those born in other continents, possibly due to genetic factors. In view of the similarities to other populations the reason for the low incidence in Israel remains obscure, and whether it may be attributed to genetic reasons or to some traditional habits remains to be confirmed
 

Background: The age-standardized incidence rate of invasive cervical cancer in Israeli Jewish women is persistently low. Selected demographic characteristics of Israeli Jewish women with cervical squamous cell carcinoma (SCC) were reported recently. 

Objectives: To assess selected clinical characteristics of Israeli Jewish women with cervical SCC.

Methods: Included were all Israeli Jewish women with SCC diagnosed during the 3-year period 2002­–2004. Data were obtained from the Israel National Cancer Registry and the Central Population Registry. Discharge summaries of the patients were reviewed and clinical data were abstracted.

Results: The study was based on 350 Israeli Jewish women with histologically confirmed cervical SCC diagnosed during the 3-year study period. The median age of the patients was 50.3 years. The most common main complaint was discharge/bleeding (35.7%) and only a small percentage (7.4%) was diagnosed subsequent to an abnormal cytological smear. The rate of patients diagnosed in stage I was 47.7%. The overall absolute 5-year survival and survival in stage I was 70% and 83.8% respectively. The rate of Israeli born patients diagnosed in stage I and their overall absolute 5-year survival was significantly higher than in the other ethnic groups.

Conclusions: Age, the most frequent main complaint, the percent of patients diagnosed in stage I and the 5-year survival (overall and in stage I) are similar to data in other countries. The survival of Israeli born women seems to be better than that of other ethnic groups.
 

Head and neck cancer is the sixth most common cancer worldwide. HNCs[1] can originate in the skin or soft tissue, in the upper aerodigestive tracts (oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, paranasal sinuses, salivary glands), or in the thyroid. In each of these sites, tumors vary not only by the primary site but also by pathophysiology, biological behavior and sensitivity to radiotherapy or chemotherapy. Management should be planned according to the tumor's characteristics, patient factors and expertise of the medical team. The main goals of therapy are ablation of the cancer while minimizing morbidity and preserving function and cosmesis. A multidisciplinary team is needed to achieve these goals. Early-stage HNC (stage I and II) should be managed with a single modality, and advanced tumors (stage III and IV) with multimodality therapy. Treatment should be directed to the primary tumor and the area of its lymphatic drainage – the neck lymph nodes. Evidence of metastases in the neck necessitates comprehensive clearance of regional lymphatic basins. However, even if there is no evidence of lymph nodes metastases, when the risk for positive neck lymph nodes exceeds 15–20% elective neck dissection is indicated. Advances in minimally invasive techniques now enable reliable microscopic and endoscopic procedures that mimic the open approaches. Development of contemporary surgical techniques and reconstructive means will help improve the quality of life of patients and prolong survival.

Background: Skin basal and squamous cell carcinomas together account for over half of all newly diagnosed cancer cases. Frozen  section control of surgical margins is often required in the head and neck region. A paraffin permanent section does not always confirm the results of a frozen section.

Objectives: To test the diagnostic accuracy of frozen section histopathological analysis in determining the free margins of excised tumors.

Methods: This was a retrospective study of 169 cutaneous basal and squamous cell carcinomas excised with surgical margins diagnosed by frozen section and confirmed by permanent paraffin sections. The data included patients' age, gender, clinical and histopathological diagnosis, as well as characteristics of the lesions.

Results: There were 149 (88%) basal cell carcinomas and 20 (12%) squamous cell carcinomas. False negative margins were found in 19 cases (11.2%) and false positive margins in 11 cases (6.6%). We did not find any correlation between false positive or false negative margins and patients' age, gender, tumor size, tumor location, or the presence of sun-damaged skin. A significantly lower rate of false negative results was found in the residual tumor group.

Conclusions: Our findings show support the use of frozen section margin control in selected patients suffering from non-melanoma skin cancer of the head and neck.