Sphincter saving and abdomino-perineal resections following neoadjuvant chemoradiation in locally advanced low rectal cancer.

BACKGROUND: The improvement in surgical techniques alongside neoadjuvant chemoradiation enabled more patients with low rectal cancer to have sphincter preservation. STUDY AIM: To compare the oncologic and functional outcome in patients with locally advanced low rectal cancer treated by neoadjuvant chemoradiation followed by sphincter saving resection (SSR) against those who underwent abdomino-perineal resection (APR). PATIENTS AND METHODS: A total of 111 patients with low rectal cancer were included in the study. Sixty-one consented patients who prospectively underwent SSR, from Jan 2008 to Jan 2013, and a retrospective group, formed of 50 patients, selected from cases seen at NCI, with comparable demographic, clinical and pathologic criteria, who underwent APR from Jan 2003 to Jan 2008. All lesions were <5 cm from anal verge. All 111 patients received preoperative chemoradiation and total mesorectal excision. RESULTS: All tumors were located at a median of 3.6 cm (range 2.5-4.5 cm) for the SSR group, and 3.5 cm (range 2.5-4.6 cm) for the APR group, from the anal verge. The median follow-up was 34 months (range 1-60 months) for both groups. The difference in disease recurrence and OS between the APR and SSR groups were both statistically insignificant. CONCLUSION: In low rectal cancer, the sphincter preservation appears to have nearly the same oncologic outcome compared to APR, this might be attributed to the small sample size and short follow up period. However, patients with sphincter preservation have certainly demonstrated an indisputable better functional outcome, in terms of stoma avoidance and adequate continence.

Evaluation of the frequency and pattern of local recurrence following intersphincteric resection for ultra-low rectal cancer.

INTRODUCTION: Abdomino-perineal resection has been the standard treatment for rectal tumors located ≤5cm from the anal verge. Recently, intersphincteric resection became a valid option which preserves the bowel continuity with better functional outcome. AIM: Is to evaluate the oncological and functional outcome alongside the associated surgical morbidity in patients with T1-3 rectal cancer, who underwent intersphincteric resection (ISR). PATIENTS & METHODS: Between the years 2006 and 2011, 55 patients with invasive rectal adenocarcinoma, T1-3 lesions, located 2-5cm from the anal verge underwent ISR with total mesorectal excision. When inevitable, complete. ISR was performed, otherwise partial ISR was done. All T3 patients underwent total meso-rectal excision (TME) while some had lateral lymph node dissection (LND) with concomitant pelvic autonomic nerve preservation (PANP). RESULTS: Among the 55 patients, 21 (38.1%) patients were T1-2 and 34 (61.9%) patients were T3. The tumor location range was 0-5cm from the anal verge (median 2.3cm). Partial or complete ISR was done for 35 (63.6%) and 20 (36.4%), respectively. Patients were followed for a median of 1.5 years (range 1-4.6 years). The 3 year local recurrence and distant metastasis free rates were 85.2% and 85.6%, respectively. All the 3 local recurrences occurred in T3 patients group, and had positive circumferential resection margins. Overall 3-year disease-free survival was 82.6%; while the overall 3-year survival was 88.7%. CONCLUSION: Intersphincteric resection with TME does not affect the local recurrence or overall survival rate in early rectal cancer T1-2 & 3, with preservation of bowel continuity and better life quality.

No correlation between radiosensitivity or double-strand break repair capacity of normal fibroblasts and acute normal tissue reaction after radiotherapy of breast cancer patients.

The aim was to study the relationship between cellular radiosensitivity or double-strand break (dsb) repair capacity of skin fibroblasts and the extent of acute reaction after radiotherapy for breast cancer. The study was performed with 25 breast cancer patients submitted to the radiotherapy unit of the Egyptian National Cancer Institute after conserving surgery. Dermal fibroblasts, established from skin biopsies, were used to determine the cellular radiosensitivity via colony assay and the capacity of dsb repair by constant-field gel electrophoresis. Acute reactions were scored using the Radiation Therapy Oncology Group (RTOG) classification. The spectrum of acute reactions varied from grade 1 to 4, whereby most patients developed a grade 1 reaction after total doses ranging between 46 and 70 Gy. Skin fibroblasts showed a pronounced variation in both cellular radiosensitivity expressed as the mean inactivation dose (Dbar) (coefficient of variation, CV=25%) as well as in the number of residual dsb (CV=33%) with no significant correlation between these two endpoints (r2=0.20, p=0.14). Both parameters did not correlate with the extent of acute reaction of the respective patient. The data obtained indicate that the sensitivity of fibroblasts measured either by colony assay or by dsb repair capacity is not a major parameter determining the extent of acute reaction after radiotherapy of breast cancer patients.

Planning of the internal mammary field based on lymphoscintigraphy localization before postoperative radiotherapy of breast cancer.

BACKGROUND: Internal mammary irradiation is still an issue of great debate. Although treatment of internal mammary lymph nodes was routinely given in the majority of randomized trials, data in its value are still limited. The aim of this study is to determine the variability of position of the internal mammary lymph nodes using lymphoscintigraphy and to compare the dose of radiation that reaches these lymph nodes, the heart and lungs if only tangential fields are used. MATERIAL AND METHODS: This is a prospective study that included 30 breast cancer patients treated in the department of radiation oncology of the Egyptian National Cancer Institute, Cairo University, planned for postoperative radiotherapy. Lymphoscintigraphy was done for all patients for detection of the exact site of the internal mammary lymph nodes. Dose volume histogram (DVH) was done to measure the dose to the heart using CT planning. Two plans were done for each patient, the first with internal mammary field (plan I), and the second without but with contralateral crossing of the midline by 1cm (plan II). RESULTS: The mean percentage of the internal mammary lymph nodes included in the internal mammary field (plan I) was 70.03% while in plan II it was 3.05%. The mean dose percentage reaching the heart in plan I was 54.5% of total dose, while in plan II it was 9.16% of total dose with significant p value<0.001. The mean dose to the heart decreased as the heart volume increased, this significant difference between the 2 plans was maintained for the different heart volumes. Also, the radiation dose to the heart in plan I varied significantly (p: 0.001) between the right side vs the left side with a mean dose of 48.02% and 63.5%, respectively. The mean dose percentage reaching the lungs in plan I and plan II was 46.53% and 24.5% respectively, with significant p value<0.001. CONCLUSION: If irradiation of internal mammary chain is intended, then a direct internal mammary field should be used. The planning of internal mammary field should be adjusted according to lymphoscintigraphy so as to include most of the draining internal mammary lymph nodes. The risk of late cardiac and pulmonary complications will increase when using direct internal mammary field, but the risk of cardiac complications will be less in irradiation of right side internal mammary lymph nodes compared to that of irradiation of the left side.

Accelerated hyperfractionation (AHF) compared to conventional fractionation (CF) in the postoperative radiotherapy of locally advanced head and neck cancer: influence of proliferation.

Based on the assumption that an accelerated proliferation process prevails in tumour cell residues after surgery, the possibility that treatment acceleration would offer a therapeutic advantage in postoperative radiotherapy of locally advanced head and neck cancer was investigated. The value of T(pot) in predicting the treatment outcome and in selecting patients for accelerated fractionation was tested. Seventy patients with (T2/N1-N2) or (T3-4/any N) squamous cell carcinoma of the oral cavity, larynx and hypopharynx who underwent radical surgery, were randomized to either (a) accelerated hyperfractionation: 46.2 Gy per 12 days, 1.4 Gy per fraction, three fractions per day with 6 h interfraction interval, treating 6 days per week or (b) Conventional fractionation: 60 Gy per 6 weeks, 2 Gy per fraction, treating 5 days per week. The 3-year locoregional control rate was significantly better in the accelerated hyperfractionation (88 +/- 4%) than in the CF (57+/- 9%) group, P=0.01 (and this was confirmed by multivariate analysis), but the difference in survival (60 +/- 10% vs 46 +/- 9%) was not significant (P=0.29). The favourable influence of a short treatment time was further substantiated by demonstrating the importance of the gap between surgery and radiotherapy and the overall treatment time between surgery and end of radiotherapy. Early mucositis progressed more rapidly and was more severe in the accelerated hyperfractionation group; reflecting a faster rate of dose accumulation. Xerostomia was experienced by all patients with a tendency to be more severe after accelerated hyperfractionation. Fibrosis and oedema also tended to be more frequent after accelerated hyperfractionation and probably represent consequential reactions. T(pot) showed a correlation with disease-free survival in a univariate analysis but did not prove to be an independent factor. Moreover, the use of the minimum and corrected P-values did not identify a significant cut-off. Compared to conventional fractionation, accelerated hyperfractionation did not seem to offer a survival advantage in fast tumours though a better local control rate was noted. This limits the use of T(pot) as a guide for selecting patients for accelerated hyperfractionation. For slowly growing tumours, tumour control and survival probabilities were not significantly different in the conventional fractionation and accelerated hyperfractionation groups. A rapid tumour growth was associated with a higher risk of distant metastases (P=0.01). In conclusion, tumour cell repopulation seems to be an important determinant of postoperative radiotherapy of locally advanced head and neck cancer despite lack of a definite association between T(pot) and treatment outcome. In fast growing tumours accelerated hyperfractionation provided an improved local control but without a survival advantage. To gain a full benefit from treatment acceleration, the surgery-radiotherapy gap and the overall treatment time should not exceed 6 and 10 weeks respectively.

Aberrant expression of cyclin A in head and neck cancer.

Cyclin A expression was studied in a series of 65 squamous cell carcinomas of the head and neck (HNSCC) and compared with known markers of proliferation, iododeoxyuridine (IdUrd) and Ki-67, to assess whether aberrant expression was prevalent. Patients had previously been administered IdUrd to study cell kinetics in relation to outcome of radiotherapy. The data showed that all three parameters were highly correlated although the absolute values were different. The median labelling indices (LI) for IdUrd, cyclin A and Ki-67 were 10.7, 17.1 and 30.8% respectively, reflecting the known pattern of differential cell cycle expression. However, there were a significant number of cases in which an unexpected relationship between cyclin A and either IdUrd or Ki-67 was present. Some of these were attributable to overexpression but others indicated underexpression. Although the greater variability and range of cyclin A expression, coupled with its more closely associated role in cell cycle regulation, might suggest that it may be a more informative marker for cell proliferation than Ki-67, the aberrant expression seen in over one third of cases would indicate that caution should be exercised in interpreting cyclin A as a surrogate marker of proliferation in HNSCC.