Management of brain metastases by whole brain radiotherapy; IMRT versus conventional RT: early results

The conventional whole brain radiotherapy is usually associated with radiation induced toxicity as alopecia, hearing deficit and neurocogenitive problems. Any effort to decrease the treatment toxicity might result in compromised target coverage with conventional therapy, thus increasing the risk of local recurrence. Intensity-modulated radiotherapy [IMRT] is a more advanced form of three-dimensional conformal radiotherapy [3D-CRT]. This approach has been demonstrated to improve tumor coverage while decreasing the dose to critical structures in the head and neck and other sites. At present there is very little clinical or dosimetric data regarding the dose distribution and outcomes from IMRT in the treatment of metastatic brain disease. This initial study was to introduce and evaluate the WBRT-IMRT as a new technique for treatment of brain metastases and to reduce the incidence and severity of radiation morbidities. The study included thirteen, consecutive adult patients with multiple brain metastases who referred to the Radiation Oncology Department in the University of Alabama at Birmingham [UAB], Birmingham, AL; USA from October 2005 till December 2005. The entry criteria were, the patients' age was 65 years or less, with Karnofesky score 70 or more, their primary malignant tumor were controlled and no evidence of extracranial disease, [eg; RTOG class I] and no definite lesions by brain MRI in the frontal or temporal lobes. The number of metastases were more than three because the department protocol was treating three or less brain metastases by streotactic radiosurgery +/- WBRT. These patients randomized between two arms. Arm A included 15 patients were treated by conventional whole brain radiation therapy [C-WBRT]. Arm B included 15 patients were treated by WB-IMRT. The conventional WBRT was given by two opposing equally weighted lateral portals by using beam eye view and multi-leaf collimator [MLC] with skin flash to protect the eyes. For the WB-IMRT plans were done using several trials of beam numbers and arrangements to get the best and most acceptable plan. The parameters for optimization included the specified dose to the PTV, the dose limits for each of the critical structures, and the respective penalties for deviation from these criteria. The PTV dose was 100% +/- 5% at the isocenter and 100% of the prescribed dose to the >99% of the CTV. The lenses were restricted at <5 Gy and also to 50% of the volume of the other OARs at 25 Gy as upper constrains. The comparison of the two plans as regard the average relative median dose to both the target volumes and the organs at risk, table 4 showed that there were no significant statistical differences between the two plans except for the scalp dose in favor of the WB-IMRT [p=0.04] while the lenses dose was lower in the C-WBRT but did not reach a significant level [p=0.06]. The radiation induced toxicity were statistically insignificant between the two treatment groups except for the frequency and severity of the alopecia which it was significantly lower in the WB-IMRT versus the conventional treatment [p-value=0.006]. The treatment outcomes in both groups were statistically insignificant and at the end of follow up period of six months progression free and overall survival were statistically insignificant [p=0.653 and 0.862 respectively]. IMRT by five field arrangement is feasible for palliative management of multiple brain metastases. An image guided approach is necessary to spare the scalp and other critical structures and to treat a reduced -margin PTV. The treatment is well tolerated and appears clinically efficient. Patients lose much less, or not at all, hair with this technique. This could have a good impact on the quality of life

IMRT planning of localized prostate cancer versus 3DCRT versus conventional RT: dosimetric study

Many trials emphasized positive local control rate and biochemical free survival with escalation of dose to the prostate in early stages of prostate cancer but the problem was the high toxicity rate of the nearby critical organs. This study was designed to compare conventional radiotherapy [RT], three-dimensional conformal radiotherapy [3DCRT] and intensity modulated radiotherapy [IMRT] for localized prostate cancer irradiation and the ability of 3DCTR and IMRT to escalate the prostate dose and at the same time reduce the dose to the rectum, bladder and small bowel in order to improve the local control rate and the tolerance of pelvic irradiation. Ten patients with stages T1c-T2b were referred for definitive radiotherapy in the Radiation Oncology Department of the University of Alabama at Birmingham, AL; USA. For each patient three treatment planning were done; the conventional plan [C-RT] was applied by initial 3-field technique then a boost by 4-field technique. The 3DCRT was applied by 6-field technique and the IMRT plan was given by 5 equally spaced fields .The total prescribed dose for the three plans was 75.60 Gy;1.8 Gy / fraction; 5fractions weekly. Three plans were compared as regard the coverage of the target volumes [GTV and PTV] and the radiation doses to the organs at risk [OARs] by means of the dose volume histogram [DVH]. The treatment planning of all plans were achieved by the use of the Eclapse machine [Varian Medical Systems, Palo Alto; CA]. The cumulative DVH of the three plans showed that both the GTV and PTV were uniformly covered by the prescribed dose and there was no significant difference between the three plans in spite that the IMRT plan was slightly better than the other two plans. As regard the nearby critical organs [OARs], the IMRT plan had the best sparing distribution and both the rectum and bladder received the lowest doses [rectum V70 and V50 were 13% and 26% respectively and for the bladder V70 and V50 were 12% and 26% respectively] versus 25% and 60% for the rectum and 18% and 28% for the bladder in the 3DCRT versus 91% and 100% for the rectum and 47% and 63% for the bladder in the C-RT plan. Moreover the IMRT plan reduced significantly the dose to the femoral heads followed by the conventional plan while the dose to the bowel in the three plans was very low and there was no difference between them. The dose escalation could be performed with IMRT to achieve increased Tumor Control Probability [TCP] while maintaining the Normal Tissue Complication Probability [NTCP] less than those from conventional and 3D conformal irradiation of the early prostate carcinoma

CMF with or without medical castration in pre-menopausal women with node positive breast cancer

The prognosis of breast cancer in young women is generally considered to be unfavorable. Thus adjuvant therapy post surgical intervention is essential in many patients especially those with high risk [e.g large tumors or positive nodes]. However the presence of steroid hormone receptors in the primary tumors of young ladies may represent a suitable target for therapy in this group of patients. In the current study 100 premenopausal women with positive axillary lymph nodes and have estrogen and/or progestrone receptor positive tumors were randomized after local therapy of the breast cancer into two groups; Group I received adjuvant chemotherapy CMF for a total of six cycles then medical castration with LHRH agonist for two years and Group II received the same chemotherapy as in group I for six cycles. Adjuvant radiotherapy was given in the majority of patients in both treatment groups. After median follow up of six years, there was no statistical significance difference between both groups as regard the disease free or overall survival P=0.537 and 0.526 respectively. The toxicity reported in both groups was quite mild with only increase in the rate of hot flashes in the medical castration group. This study confirm the safety and tolerability of addition of medical castration to adjuvant chemotherapy which can be easily accepted by young women because of its reversible action, however it didn't answer many important questions about the optimum duration of ovarian suppression and the need for combined hormonal therapy like addition of tamoxifen to ovarian castration and sequence of different therapy

Combined modality [chemotherapy and radiotherapy] versus radiotherapy alone in the management of locally advanced head and neck cancer

Generally radiotherapy alone or combined with surgery for locally advanced head and neck epidermoid carcinoma yields poor results. This study was designed to assess the therapeutic efficiency of combined modality treatment [neoadjuvant chemotherapy and radiotherapy] versus radiotherapy alone in the management of locally advanced head and neck cancer and to evaluate its impact on the progression free and overall survival. Three cycles of cisplatin [100 mg/m[2]] day I and 5-fluorouracil [1 gm/m[2]] days 1-3 repeated every 21 days were given for 30 untreated patients followed by radiation therapy. This arm [group I] was compared with radiation therapy alone In another 30 patients [group II]. These patients had stages III and IV disease with performance of 70=70% and with a minimum followed up of 18 months. In group I neoadjuvant chemotherapy induced complete response [CR] in seven patients [23.3%] and partial response [PR] in 19 patients [63.3%]. After the addition of radiation therapy, CR increased to 56.7%. In the radiotherapy alone group. CR and PR were 40% and 43.3% respectively The difference between both arms as regards the overall response was not statistically significant [p=0.704]. The chemotherapy schedule was tolerable but it increased the acute radiation reactions to the extent that eight patients could not tolerate the boost radiation dose. The progression free survival [PFS] of responders in the combined treatment arm was 52% compared with 44% in radiation alone ann. The median time to progression was 8.2 months versus 7.3 months in both arms respectively. The overall survival [OS] was higher in the combined treatment arm but not statistically significant [p>0.05]. Neoadjuvant chemotherapy could improve the response rate and OS with acceptable local and systemic toxicity. Accrual of large number of patients and longer follow up period is needed to emphasis the advantageous effect of neoadjuvant chemotherapy