Issue No. 2 - Jul 2007
8-16 The role of concurrent chemo-radiotherapy in patients with head and neck cancers: a review
   M.D. Al-Sarraf1
1 Williams Beaumont Hospital, Royal Oak, Michigan, USA
    In the past, radiotherapy alone was the “traditional” and the standard single treatment for patients with unresectable and/or inoperable locally advanced head and neck cancers. Because of the poor results obtained with this approach in these patients, concurrent chemotherapy and radiation therapy has been investigated since the 1960s (1, 7). The rationale for such treatment is to increase local control by overcoming radio-resistance and to eradicate systemic micro-metastasis. The most significant potential mechanisms of interaction between chemotherapy and radiation therapy are summarized in Table 1.

Initially, agents like methotrexate, hydroxyurea, 5-fluorouracil (5FU), or bleomycin were tested in combination with radiation therapy. Since each of these drugs produces mucositis and stomatitis, the local side effects of radiation therapy on the oral and oro-pharynx mucosa were increased, which resulted in poor patient compliance, more interruptions of radiotherapy, and no improvement in overall survival when compared to radiation therapy alone. Other important factor that resulted in not detecting survival advantage with the combined approach is the small number of patients randomized to each group that was unable to detect small but important differences of + 10%.

Platinol compounds (cisplatin, carboplatin) alone do not induce mucositis and does not increase the local toxicity of mucositis of radiation therapy in patients with head and neck cancers. It is probably the best currently available radio-sensitizer, and it possesses all the mechanisms of interaction with radiation therapy that are summarized in Table 1. The clinical CR rate obtained with concurrent cisplatin and radiation therapy (single daily fraction) in patients with locally advanced head and neck cancers is in the range of 65% to 70% (2, 7). The majority of the patients in these studies had stage IV disease. Cisplatin has been administered in various schedules: weekly, daily, days 1-5 every 4 weeks, and every 3 weeks. One randomized ECOG/RTOG trial with weekly administration of cisplatin at 20 mg/m2 during radiation therapy vs. radiation therapy in locally advanced patients was negative (8). The addition of another agent or agents in combination with cisplatin (i.e., 5FU or taxanes) concomitant with radiation therapy did not add to the clinical CR rate but increased in the local side effects, especially mucositis (3, 4, 9, 10, 11) [Table 2]. Thus, cisplatin alone appears to be the chemotherapeutic drug of choice for concurrent chemotherapy with radiation therapy in patients with head and neck cancers. At the present time, cisplatin alone given on a 3-week schedule is the most widely used in the United States.

Carboplatin, the second-generation platinum drug, possesses all of the radio-potentiation properties of cisplatin but has a different side effect profile. Carboplatin is used in a weekly schedule concurrent with radiation therapy in patients with head and neck cancers. The clinical CR rate reported in phase II studies with concomitant carboplatin and radiation therapy (single daily fraction) is in the range of 65% and 70%, which is similar to the clinical CR rate reported with cisplatin and radiation therapy (2,3,11) [Table 2]. For the last 15 years, our personal practice has been to use carboplatin rather than cisplatin in our concurrent chemotherapy and irradiation treatment, using a weekly dose of an AUC of 1.5 after induction chemotherapy or in the dose of AUC 2.0 without initial chemotherapy. In a comparison of radiation therapy alone or with either cisplatin or carboplatin in these patients, two randomized trials reported the superiority of either combination arms to the radiation therapy alone arm, with no statistical difference between the two combination arms (11, 12).

Mitomycin C also possesses most of the radiopotentiation mechanisms of interaction with radiation therapy [Table 1]. Randomized trials comparing radiation therapy with or without mitomycin C showed improved local control but no differences in overall survival between the two groups (3). More recently, gemcitabine and the taxanes have been tested for their radio-sensitizing effects. The clinical CR rate for the combination of taxanes alone or with other agents given concurrently with radiation therapy is approximately 65% (3, 6, 9, 10). However, the local side effects, especially mucositis, are problematic.
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2 17-28 Epidemiology of thyroid cancer: a review with special reference to Gulf Cooperation Council (GCC) states
    A. S. Al-Zahrani1, 2, K. Ravichandran2
1 Gulf Center for Cancer Registration,
2 Biostatistics & Epidemiology Department, King Faisal Specialist Hospital & Research Center, Riyadh, Kingdom of Saudi Arabia.
    A wide variation in incidence of thyroid cancer according to age, sex, ethnicity and geographic region was observed. In general, it occurs more frequently in women than men and a substantially higher rate was observed particularly during fertile period of women compared with men of the same age. Papillary carcinoma is the most prevalent histological type, irrespective of gender and conditions like iodine level. Over the years the incidence of thyroid cancer, especially papillary type, increases around the world. Ionizing radiation, in particular radiotherapy to head and neck region was the most established risk factor for thyroid cancer. Goiter, miscarriage or abortion (particularly in the first pregnancy) may also predispose to thyroid cancer risk. Cigarette smoking and use of contraceptives may be modifier of thyroid cancer risk. In all the GCC states thyroid cancer is the second most common cancer except in Bahrain and Kuwait (where it stands third).

During the five year period (1998-2002) 549 male and 1898 female thyroid cancers were diagnosed in all the GCC states. Papillary carcinoma is the predominant histological type followed by follicular carcinoma in both gender. Among female, Qatar has the highest incidence with an age standardized incidence rate of 13.5 per 100,000 followed by Kuwait (7.7), Bahrain (7.6), Emirates (6.0), Oman (5.9), and Saudi Arabia (5.0). There were at least 2.6 female thyroid cancer cases (in Kuwait) for each male thyroid cancer case and this goes up to 6.6 in Bahrain. Incidence of thyroid cancer in the GCC states is closer or higher than that of some of the developed countries.
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3 29-32 Spinal cord compression, an overview for radiation oncologists

S. Abuzallouf
Department of Radiation Oncology, Kuwait Cancer Control Center

    Spinal cord compression is a major cause of morbidity and or mortality in a cancer patient. This is one of the few oncologic emergencies, as delay in therapy leads to frank paralysis. Several key areas must be considered in the diagnosis and management of spinal cord compression. Because the outcome can be devastating, a diagnosis must be made early and treatment initiated promptly. The purpose of this paper is to present an overview of the important points to radiation oncologists regarding the management of spinal cord compression in an evidence-based approach.
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4 33-41 131I-mIBG in the diagnosis of primary and metastatic neuroblastoma
    T. El- Maghraby
Nuclear Medicine Section- Radiology Department, Saad Specialist Hospital, Al-Khobar, Saudi Arabia
    Objective: Neuroblastoma is the third most common malignancy of childhood. 131I-MIBG scintigraphy must be performed in patients with neuroblastoma at the time of staging. The aim of this study is to identify the role of 131I-MIBG scintigraphy in neuroblastoma patients in corrrelation with other diagnostic modalities for staging of the disease.

Methods:  Twenty six patients provisionally diagnosed by clinical and imaging criteria to have neuroblastoma were included. On histopathologic verification 5 of these 26 patients were rediagnosed as non-neuroblastoma. Each patient had imaging by ultrasound, CT and/or MRI. In all cases, 131I-MIBG scintigraphy was performed, among them 15 patients had additional 99mTc- MDP bone scan.

Results: The outcome demonstrated that CT and MRI were able to detect lesions in 19 out of 21 patients; while in 2 patients no lesions were detected. 131I-MIBG showed active lesions in 16 out of the above 19 patients, while in 3 patients 131I-MIBG was negative. There were no false positive result by 131I-MIBG scan. Accordingly, 131I-MIBG is able to detect neuroblastoma lesions with an overall sensitivity of 84.2%, specificity of 100% and an accuracy of 85.7%. Detection of primary lesions by 131I-MIBG was significantly better than 99mTc-MDP bone scanning (92.31% vs. 61.54% respectively) (P < 0.05). For skeletal metastases, 131I-MIBG scan has a higher ability to detect more lesions than 99mTc-MDP bone scan (P=0.023).

Conclusions: 131I-MIBG scintigraphy has an excellent ability to discriminate between neuroblastoma and other small round cell paediatric tumours. 131I-MIBG was found to be significantly superior to conventional bone scanning in revealing both primary and metastatic osseous lesions.
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5 42-46 Hook wire localization procedure in biopsy and diagnosis of early breast cancers: Oman experience

T. Al-Lawati1, S. Al-Mammary1, H. Nahar1, M. Mateen1, S. Thomas2, F. Al-Lawati2, D. Samarasinghe2,
S. Al-Belushi
3, and A. Darwish3
1Department of General Surgery, 2Department of Histopathology, 3Department of Radiology,
Royal Hospital, Sultanate of Oman

    Between January 2000 and December 2005, a total of 30 cases of impalpable suspicious breast lesions (microcalcifications or impalpable lumps classified as BIRADS IV and above) were biopsied after hook wire localization. This is a retrospective review of these cases. Results: One third of the suspicious lesions were malignant or pre-malignant. All these have further oncological treatment and follow up.

Conclusions: • Hook wire localization biopsy remains an important tool for the diagnosis of impalpable lesions of the breast; • The incidence of malignancy in our series was similar to the published international levels; • Our series is small, so there is a need to review the data with bigger number.
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6 47-54 Prognostic index for primary adenocarcinoma of the urinary bladder

M. S. Zaghloul 1,3, M. El Baradie 3, Nouh 2,4, S. Abdel-Fatah 1, 4, A. Taher 1 and M. Shalaan3
1 Radiation Oncology Dept., 2 Pathology Dept., 3 Surgical Oncology
Dept., National Cancer Institute, Cairo 4 Minia Oncology Centre, Egypt

    Aim: To determine the working independent prognostic factors and the prognostic index of adenocarcinoma of the urinary bladder. The effect of adding postoperative radiotherapy to radical cystectomy on this prognostic index was also investigated.

Patients and Methods: Two hundred and sixteen patients having adenocarcinoma of the urinary bladder were treated with radical cystectomy and pelvic lymphadenectomy with (82 patients) or without (134) postoperative radiotherapy. Postoperative radiotherapy (PORT) was given to the whole pelvis in a dose of 50 Gy /25 fractions over 5 weeks, and started 4-10 weeks after surgery.

Results: The 5-year disease-free survival rate was 44 ± 4% for the whole group. Postoperative radiotherapy improved the disease-free survival significantly from 33 ± 6% for cystectomy alone to 58 ± 6% for PORT patients (P=0.002). The independent prognostic factors for DFS were the pathological stage, histological subtypes, nodal involvement and the addition of postoperative radiotherapy. The stratification of patients using prognostic indices according to the pathological findings produces identifiable prognostic groups. Postoperative radiotherapy improved the DFS significantly in the intermediate and high risk indices (p=0.0004 and 0.0002 respectively).

Conclusions: The identified prognostic indices with their prognostic group could be used not only as a predictor of disease-free survival but also as a good predictor for the need to add adjuvant therapy in adenocarcinoma of the urinary bladder.
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7 55-64 Neoadjuvant chemotherapy in locally advanced non-small cell lung cancer
    W. Hamouda, Y. Dorgham , A. Yosry, and M. Abdel Wahab
Department of Radiation Oncology, Faculty of Medicine, Zagazig University
    Objective: The objective of this study was to evaluate the role of neoadjuvant chemotherapy in the treatment of locally advanced non small cell lung cancer (NSCLC) followed by radiotherapy versus radiotherapy alone.

Material and Methods: Sixty nine patients were randomized to chemotherapy (group A) or radiotherapy alone (group B). The induction chemotherapy consists of cisplatin (80 mg/m2) day 1 and Gemcitabine (1250 mg/m2), infusion day1 and 8. Cycles were repeated every 3 weeks. Radiotherapy was given 4-6 weeks after chemotherapy to a dose of 60 Gy/30 fractions/6 weeks.

Results:  A total of 66 patients were evaluable for response; 34 in group A and 32 in group B. The overall response rate was 41.2% for group A and 21.8% for group B (P<0.5) but with no complete response observed in either group. At a median follow up of 15 months, the overall survival was 65% and median survival was 12 months for group A. However in group B the overall survival at 15 months was 30% and the median survival was 9 months (P<0.001). Treatment toxicity in group A was mainly haemotological in 79% of patients none of them was grade III or IV. Grade III Nausea and vomiting was reported in 73.5% of patients, grade I esophagitis in 5.8% of patients, grade I, II radiation pneumonitis in 26.4% of patients. Alopecia was observed in 29.4% of patients, nephrotoxicity in 17.4%. Treatment toxicity in group B were generally less than in group A but not statistically significant except for grade III vomiting (15.6%) and alopecia (0%).

Conclusion: Combination chemotherapy of cisplatin and gemcitabine is a tolerable and active induction chemotherapy regimen for patients with locally advanced NSCLC. Sequential radiotherapy given after induction chemotherapy is tolerable and offers a hope of improved locoregional control and survival compared with radiotherapy alone.
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8 65-68 Case report of long term survivor of metastatic cloacogenic carcinoma of the anal canal with chemotherapy

S. Fayaz, S. Vasishta, M. Motawy
Department of Radiation Oncology, Kuwait Cancer Control Center (KCCC)

    A fifty-two years old Egyptian lady, case of cloacogenic carcinoma of anal canal with extensive liver metastasis showed complete remission with 5-Fluorouracil (5FU) And Cis-Dichlorodiammineplatinum (CDDP) chemotherapy only and remains disease free five & half years after therapy.
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9 69-72 A ruptured retroperitoneal germ cell tumor with invasion into the duodenum: a case report
    W. Al Masri, A. Alhendal, M. Al Mishaan
Department Of Surgery, Al- Sabah Hospital, Kuwait
    We report a rare case of a retroperitoneal germ cell tumor in a 31 years old male who presented with an acute abdomen. He gave a six-months history of back pain and significant weight loss. Clinical examination and ultrasound of the testes didn’t show any primary focus. Intraoperative findings showed a retroperitoneal midline mass that has ruptured into the peritoneal cavity and has invaded into the duodenum. The final pathology revealed a yolk sac tumor. We present this rare case of a primary para-aortic extragonadal yolk sac tumor and the differential diagnosis of a retroperitoneal mass.
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