Implications of p53 over-expression in the outcome with radiation in head and neck cancers.

BACKGROUND: Abnormalities in the p53 tumor suppressor gene and in the expression of its protein are commonly seen in several tumors. The prognostic implication of these p53 abnormalities was studied in 55 patients with advanced head and neck cancers. PURPOSE: To identify p53 as a prognostic factor in assessment of response and survival outcome to radiotherapy in head and neck malignancies. MATERIALS AND METHODS: This prospective study was carried out from April 1998 to December 1999. Fifty five patients with proven squamous cell carcinoma of the head and neck region were treated by radiotherapy (RT) (n=34) with or without chemotherapy (CT) (n=21). A dose of 70 Gy/35#/7 weeks was given with or without concurrent administration of weekly cisplatin (35 mg/m2). Paraffin sections obtained at the time of diagnosis, were examined immunohistochemically for p53 overexpression with monoclonal antibody DO-7 (DAKO). The scoring of p53 positive cells was carried out by a trained pathologist. Selected areas of p53 positive cells were viewed under high power field for quantitative assessment of the p53 over expression. A minimum of 1000 cells were counted and the labeling index (LI) was calculated in terms of percentage of p53 positive cells over the total number of cells counted. A 10% nuclear reactivity exhibiting chromogen positivity cutoff point was established. OBSERVATIONS: The data was analyzed as of January 2006. Median follow-up of all the patients was eight months (1-95 months). The median age of this study group was 58 years and of the 55 patients, 48 were males. Positive expression of p53 gene protein was documented by immunohistochemistry in 24 (44%) patients. Over expression of p53 was not associated with T or N stage, site of disease, radiation response or survival outcomes (P=0.143). Stage was the only independent prognostic variable, both for the response to treatment (radiation) and survival (P=0.01). CONCLUSIONS: Over expression of p53 protein, when detected immunohistochemically, does not predict for radiation response in these tumors.

Variations in clinical estimates of tumor volume regression parameters and time factor during external radiotherapy in cancer cervix: does it mimic the linear-quadratic model of cell survival?

BACKGROUND: Tumor regression parameters and time factor during external radiotherapy (EXTRT) are of paramount importance. AIMS: To quantify the parameters of tumor regression and time factor during EXTRT in cancer cervix. SETTINGS AND DESIGN: Patients, treated solely with radiotherapy and enrolled for other prospective studies having weekly tumor regressions recorded were considered. MATERIALS AND METHODS: Seventy-seven patients received 50 Gy of EXTRT followed by intracavitary brachytherapy. Loco-regional regressions were assessed clinically and regression fraction (RF) was represented as RF=c + a 1D + a 2 D2 sub - a 3T, with c, D and T as constant, cumulative EXTRT dose and treatment time respectively. STATISTICAL ANALYSIS USED: Step wise linear regression was performed for RF. Scatter plots were fitted using linear-quadratic fit. RESULTS: Coefficients of parameters D, D2 sub and T were computed for various dose intervals, namely 0--20 Gy, 0--30 Gy, 0--40 Gy and 0--50 Gy. At 0--20 Gy and 0--30 Gy, only the coefficient of D2 was significant (P 2 sub and T turned significant (P 2 sub and T showed significance, leading to an estimate of 26 Gy for a1/a2 and 0.96 Gy/day for a3/a1. CONCLUSIONS: As with alpha/beta and gamma/alpha of post-irradiation cell survival curves, a1/a2 and a3/a1 represents the cumulative effect of various radiobiological factors influencing clinical regression of tumor during the course of EXTRT. The dynamic changes in the coefficients of D, D2 sub and T, indicate their relative importance during various phases of EXTRT.

Early occurrence of acute myeloid leukemia following adjuvant radiotherapy and higher cumulative dose of cyclophosphamide in carcinoma breast.

We report a case of cancer breast developing acute myeloid leukemia (AML) within a relatively short interval of two and a half years of her primary treatment. This could be attributed to post operative radiotherapy and a higher cumulative dose of cyclophosphamide (14.4 gm) which had to be given as a part of her combination chemotherapy regimen, initially as adjuvant and then later as salvage chemotherapy. The successful salvage therapy for secondary AML instituted in this case is also discussed.

Tumor regression dynamics with external radiotherapy in cancer cervix and its implications.

BACKGROUND: To study the external radiotherapy (EXTRT) regression patterns in cancer of the cervix. AIMS: Evaluate EXTRT tumor regression doses (TRD) for 50% (TRD50), 80% response (TRD80), normalized dose response gradient (g50) and slope (slope50) with clinical outcome. SETTINGS AND DESIGN: Patients, treated solely with radiotherapy and enrolled for other prospective studies having weekly tumor regressions recorded were considered. MATERIAL AND METHODS: Seventy-seven patients received 50Gy of EXTRT at 2 Gy/fraction followed by 18Gy of high-dose rate intracavitary brachytherapy at 6 Gy/fraction. Loco-regional regressions were assessed clinically at weekly intervals during EXTRT to generate EXTRT dose-response curves. STATISTICAL ANALYSIS USED: Student's t test, logistic regression, Kaplan Meier and Cox's proportional hazard model. Scatter plots were fitted using cubic fit. RESULTS: Age (P=0.052) and absence or presence of gross residual tumor (AGRT and PGRT respectively) following EXTRT (P<0.001) were the only determinants for complete response (CR) at 1 month following completion of radiotherapy. EXTRT tumor regression sigmoid curves obtained for various patient characteristics differed only for those with AGRT and PGRT with differences in TRD50, (P<0.001); TRD80 (P<0.001) and slope50 (P=0.001). Response status to EXTRT was a prognosticator for loco-regional disease free survival (LDFS) (AGRT vs. PGRT; P=0.046). On multivariate analysis, both TRD50 and TRD80 emerged as significant predictors for tumor status at end of EXTRT while TRD80 was the sole determinant of LDFS. CONCLUSION: Extent of tumor regression to EXTRT is an important predictor for treatment outcome in cancer cervix as evident from TRD50 and TRD80 values of EXTRT tumor regression curves.

Summated chemotherapy dose-intensity versus loco-regional response in locally advanced breast cancer: its possible implications.

BACKGROUND: Summated dose-intensity (SDI) of chemotherapy regimen could influence the outcome in malignancies. AIMS: To evaluate the implication of SDI and identify key drugs for loco-regional response in locally advanced breast cancer (LABC). Settings and design: This retrospective study was based on audit of records of LABC patients who had received neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: Actual unit dose-intensity (UDI) of each drug and corresponding SDI of every doxorubicin (n=116 cycles) or non-doxorubicin (n=110 cycles) based NACT received by 42 patients of LABC were summated. Cumulative dose-intensity (CDI) for individual drugs and cumulative SDI (CSDI) for the entire course of NACT were estimated and correlated with quantum of primary tumor, axillary and supraclavicular nodal responses. STATISTICAL ANALYSIS USED: Two-sided chi-square, t-test, step-wise regression was used. RESULTS: Dose-response curve between CSDI and corresponding responses for both primary and lymph nodes were sigmoid in shape for both doxorubicin or non-doxorubicin based NACT. Curves were best fitted using a cubic fit for all patients (r2 = 0.82, 0.84 and 0.93 for primary tumor, axillary and supraclavicular lymph nodes respectively). CSDI emerged as an important prognosticators for both primary (P<0.001) and nodal (P<0.001) responses. Individually, CDI of 5-fluorouracil for primary (P<0.001), CDIs of doxorubicin (P<0.001) and methotrexate (P=0.006) for axillary nodes and CDI of cyclophosphamide (P=0.001) for supraclavicular nodes were significant. CONCLUSIONS: Loco-regional responses in LABC are dependent on CSDI of NACT regimen. Drugs for high-dose intensification protocols could be identified and chosen based on the impact of CDI of individual drugs in NACT.

Primary CNS lymphoma: an audit of cases treated over a nine year period and review of the literature.

Primary CNS lymphoma is a rare tumor comprising around one percent of all brain tumors. This report is an audit of eight cases [5 males, 3 females, age range: 17-55 years] which were accrued over nine years. All patients underwent surgical decompression, followed by radical Radiotherapy [RT]. Five out of eight patients received adjuvant chemotherapy in the form of CHOP or PCV. Of the patients who relapsed two received CHOP as a salvage therapy, one received PCV therapy and lomustine with intrathecal methotrexate. At a median follow up of 16 months [range 1 to 39 months] the two year disease free survival and overall survival were 13 percent and 38 percent respectively, which is in accordance with the literature. High dose RT to whole skull with boost therapy is indicated for all the cases. However, the role of chemotherapy and the appropriate regime needs to be defined with certainty.

Adjuvant therapy in invasive thymoma: an audit of cases treated over an 8 year period.

Invasive thymomas comprise 0.1%-0.2% of all malignancies in India. This report is an audit of 11 cases (10 males and 1 female) at a mean age of 36.6 years (range 25-52 years) of invasive thymoma accrued over an eight year period treated by combined modality treatment. Nine of these presented with myaesthenia gravis. All patients underwent initial surgery (3 partial and 8 total resections) and postoperative radiotherapy. Two of the three partially resected patients received one course of chemotherapy prior to radiotherapy consisting of cyclophosphamide, vincristine, procarbazine and prednisolone. At a median follow up of 28 months (range 2-87) there have been no local relapses, one distant metastasis and one death due to uncontrolled myaesthenia. The treatment strategies with invasive thymomas would depend upon the extent of resection. Postoperative radiotherapy appears to be indicated in all cases, however the role of chemotherapy may be limited to those with partial resection.

Actinomycosis mimicking carcinoma of the maxillary sinus.

Human actinomycosis may pose a diagnostic problem at times and is often mistaken for a neoplasm. A thirty-five year old male was clinically diagnosed as a case of carcinoma of the right maxillary sinus on the basis of history, clinical presentation and radiologic findings. Tissue biopsy was negative for malignancy on three consecutive occasions. Microscopic examination showed bits of granulation tissue and fragments of filamentous structures. On microbiological examination, Actinomyces israelii was isolated and fungus culture was negative. Long term Penicillin treatment caused disappearance of all signs and symptoms. The report highlights the importance of bearing in mind the fact that certain rare, chronic, suppurative granulomatous infections, like actinomycosis, may mimic malignancy.

Giant cell tumour of the petrous bone.

Giant cell tumours (GCT) are rare in the skull bones. In the cranium the sphenoid bone is the most common site. The petrous bone is a very uncommon location for such tumours. The chance location of GCT at the base of the skull makes total surgery difficult and hazardous. A case of GCT of the petrous bone is presented. The clinical course in the patient and role of primary radiotherapy in GCT in such an unusual site is discussed.

Evaluation of electron beam irradiation technique in Indian breast carcinoma patients.

A technique for post-mastectomy irradiation in breast cancer patients is described. The chest wall and internal mammary nodes are irradiated with single, anterior electron beam. The axillary and supraclavicular nodal regions are treated with parallel opposed telecobalt beams. A total of 124 patients have been subjected to this procedure. All, except five, completed the treatment. Desquamation, dry as well as wet, was of universal occurrence in electron irradiated zones. The follow up period is 2-26 months with a median of 12 months. Out of the 106 followed up patients, two developed local recurrence while distant metastases were observed in 13 patients.