Impact of Pathologic Complete Response following Neoadjuvant Chemotherapy ± Trastuzumab in Locally Advanced Breast Cancer.

PURPOSE: This study was designed to examine the relationship between breast cancer molecular subtypes and pathological response to neoadjuvant chemotherapy (NAC) ± trastuzumab, in locally advanced breast cancer (LABC). METHODS: Female patients with LABC (T2-T4, N0-N2, and M0) who received neoadjuvant chemotherapy + trastuzumab if HER2+ subtype, followed by surgery and radiotherapy ± hormonal therapy, were identified. The primary endpoint was pathologic complete response (pCR) in the breast and axilla (ypT0/ypN0), with final analysis on disease-free survival (DFS) and overall survival (OS). RESULTS: Six hundred eighty-one patients with a median age of 44 years, premenopausal: 70%, median tumour size: 7.0 cm (range 4-11 cm), stage II B: 27% and III A/III B: 73%, ER+/HER2-: 40.8%, ER-/HER2-: 23%, ER+/HER2+: 17.7%, and ER-/HER2+: 18.5%. Overall pCR (ypT0/ypN0) was 23%. The pCR rates based on molecular subtypes were ER+/HER2-: 9%; ER+/HER2+: 29%; ER-/HER2-: 31%; and ER-/HER2+: 37%. At median follow-up of 61 months, ER+/HER2+ and ER+/HER2- subtypes had the best 5-year DFS and OS; meanwhile, ER-/HER2+ and ER-/HER2- subtypes had the worst. CONCLUSION: Women with ER+/HER2- disease are the least likely to achieve pCR, with the highest rates in HER2+ and triple-negative subgroups. Degree of response is associated with OS; despite the comparatively higher likelihood of achieving pCR in ER-/HER2+ and triple-negative, these subgroups experience a survival detriment. We are consistent with the published data that patients who attain the pathological complete response defined as ypT0/ypN0 have improved outcomes.

Volumetric-modulated arc therapy (VMAT) versus 3D-conformal radiation therapy in supra-diaphragmatic Hodgkin's Lymphoma with mediastinal involvement: A dosimetric comparison.

PURPOSE: To compare volumetric-modulated arc therapy (VMAT) with 3D-conformal radiation therapy (3D-CRT) mediastinal irradiation for stage I-II supra-diaphragmatic Hodgkin's Lymphoma (HL). PATIENTS AND METHODS: Eleven patients were planned for RT after 4-6 cycles of ABVD chemotherapy: conventional 3D-CRT (AP/PA) and VMAT plans were conformed to the same PTV. Objective was to choose the best PTV coverage plan with the least OAR dose. The 2 plans were compared for: PTV coverage, mean dose and V5,V20lung, mean dose and V30heart, V5, V10, V15breast (female patients), and the integral body dose. RESULTS: Both techniques achieved adequate PTV coverage. Mean lung and heart dose was consistently lower in VMAT plans. The lung V20 dose was acceptable for VMAT, but exceeded the tolerance threshold in 6 cases with 3DCRT plans. A mean difference of 15.9% for both lungs V20 favored VMAT plans; average MLD difference was 2.3Gy less for VMAT plans. Similarly, lower maximum and mean heart doses with a 3.3Gy dose reduction and a 9.4% difference in V30 favored VMAT plans. Mean V5lung/female breast and integral dose were invariably higher in VMAT plans because of the low-dose spread. CONCLUSIONS: VMAT is a valuable technique for treatment of large mediastinal HL. VMAT spares the lung and heart compared to 3DCRT using ISRT in select HL cases. VMAT allows dose escalation for post-chemotherapy residual disease with minimal dose to OARs. VMAT low radiation dose (V5) to the normal tissues, and the increased integral dose should be considered.

Among 45 variants in 11 genes, HDM2 promoter polymorphisms emerge as new candidate biomarker associated with radiation toxicity.

Due to individual variations in radiosensitivity, biomarkers are needed to tailor radiation treatment to cancer patients. Since single nucleotide polymorphisms (SNPs) are frequent in human, we hypothesized that SNPs in genes that mitigate the radiation response are associated with radiotoxicity, in particular late complications to radiotherapy and could be used as genetic biomarkers for radiation sensitivity. A total of 155 patients with nasopharyngeal cancer were included in the study. Normal tissue fibrosis was scored using RTOG/EORTC grading system. Eleven candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were selected for their presumed influence on radiosensitivity. Forty-five SNPs (12 primary and 33 neighboring) were genotyped by direct sequencing of genomic DNA. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107). Results showed statistically significant (P < 0.05) association with radiation complications for six SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). We conclude that these six SNPs are candidate genetic biomarkers for radiosensitivity in our patients that have cumulative effects as patients with severe fibrosis harbored significantly higher number of risk alleles than the controls (P < 0.001). Larger cohort, independent replication of these findings and genome-wide association studies are required to confirm these results in order for SNPs to be used as biomarkers to individualize radiotherapy on genetic basis.

Utilization of radiotherapy services by a palliative care unit: pattern and implication.

BACKGROUND: The role of radiotherapy in palliation is well recognized. Analyzing referrals from an inpatient palliative care unit (PCU) to the radiation oncology (RO) service may help in planning palliative care (PC) services and educational programs. OBJECTIVE: To determine the pattern and rate of referrals from a PCU to the RO service at a tertiary oncology facility in Saudi Arabia. METHODS: Referrals from the PCU to the RO service were prospectively identified over the period beginning November 27, 2007 and ending March 9, 2011. The appropriateness of referrals was determined by 2 radiation oncologists. RESULTS: Of the 635 cancer admissions to the PCU, 25 (3.9%) referrals to RO were made, and 32 sites were irradiated. All patients had a poor performance status (ECOG > or = 3). The most common areas irradiated were vertebrae (40.6%), pelvis (18.7%) and other bony structures (28.1%). Pain control was the most frequent reason for referral (87.5%). Only one referral was regarded by the RO service as inappropriate, indicating that 96% of the referrals were appropriate. The mean time lapse between referral and starting radiation was 4 +/- 3.6 days. A total of 75% of the patients died in the PCU within a median of 30 days post radiotherapy. CONCLUSION: The small minority of patients in the PCU referred for radiotherapy were deemed appropriate referrals by the radiation oncologists despite their poor performance status and limited time remaining. When planning a PCU with similar admission criteria, the availability of a radiotherapy facility in close proximity may not be a priority.

Association between XRCC1 G399A Polymorphism and Late Complications to Radiotherapy in Saudi Head and Neck Cancer Patients.

BACKGROUND: It has been hypothesized that patient to patient variation in normal tissue reactions to radiotherapy is associated with the presence of polymorphic variations in genes involved in DNA repair. PURPOSE: To test for a possible association between two single-nucleotide polymorphisms (SNPs), XRCC1 399 G>A Arg/Gln and XRCC3 241 C>T Thr/Met and late reactions to radiotherapy. PATIENTS AND METHODS: In this case control study, 50 Head and Neck cancer patients were retrospectively recruited. The grade (G) of fibrosis, a late complication to radiotherapy, was scored using the RTOG/EORTC grading system. Radiosensitive patients with moderate to severe subcutaneous and deep tissue fibrosis (cases, G2-3, n=25) where matched with patients with minimal fibrotic reactions (control, G0-1, n=25). The two nonsynonymous SNPs were genotyped by direct sequencing of DNA extracted from blood or cultured fibroblasts. RESULTS: Allelic frequency showed significant association with grade of fibrosis for XRCC1 399 G/A (p=0.05), but not for XRCC3 241 C>T (p=0.10). CONCLUSIONS: This pilot study corroborates the association between XRCC1 399 G>A and risk of late normal tissue complications following radiotherapy in our patients. Large studies are required to unravel more SNPs that can influence radiosensitivity and ascertain the associations with reactions to radiotherapy in order to be used as genetic predictive biomarkers of individual radiosensitivity. KEY WORDS: Single nucleotide polymorphism - Radiosensitivity - Late reactions to radiotherapy - XRCC1 - XRCC3.

Renal cell carcinoma in children. Prognostic factors.

OBJECTIVE: To determine the outcome in childhood renal cell carcinoma and the role of surgical and radiation treatment. METHODS: The records of 21 children with renal cell carcinoma were reviewed, 15 patients treated in the University of Toronto centers from 1959 through to 1997 and 6 patients treated in King Faisal Specialist Hospital, Riyadh, Kingdom of Saudi Arabia from 1975 through to 1998. The age was 3-17 (median 13) years. Systematic metastases were present at diagnosis in 5 patients. Regional nodal spread was present in 9 patients and 7 patients had localized disease alone. In the 16 M0 patients, the surgical treatment was radical nephrectomy (14 patients) partial nephrectomy (one patient) and wedge resection (one patient). Postoperative radiation treatment was utilized in 8 (50%) of these patients. RESULTS: The 5 year survival rate for all patients was 52%, and for M0 patients was 70%. No patient with systematic metastases at diagnosis survived beyond 26 months. Four of 7 node negative patients and 8 of 9 node positive patients remained in first complete remission, with the duration of follow up 1-30 (Median 5) years. Seven of 8 M0 patients who did not receive adjuvant radiation therapy continued in first remission (3N0, 2NI, 2N2), compared with 5 of 8 patients who received postoperativeradiation treatment (1 N0, 2 NI, 2 N2). CONCLUSION: The prognosis of localized renal cell carcinoma in childhood may be better than in the adult. Gross complete resection is required for long term survival. Elective postoperativeradiation treatment is not indicated.