T-level downstaging and complete pathologic response after preoperative long-term radiochemotherapy for locally advanced rectal cancer

Advantages of neoadjuvant chemoradiotherapy for locally advanced carcinoma of the middle and the lower third of the rectum are downstaging and downsizing of the tumor. Results of pathologic results are affected by post-treatment tissue changes and may influence the choice of surgical procedure. Forthy-three consecutive patients (27 male, 16 female; mean age 64 years) were operated after receiving a long-term chemoradiotherapy during a period of 16 months. The data of initial staging procedure (high resolution magnetic resonance imaging) and results of pathological examination of the surgical specimens were analyzed. Regression of tumor was assessed by the absence of vital tumor cells and the post-treatment fibrotic tissue alterations. Regression of tumor size was seen in 42/43 patients leading to an improved T-stage in 27 patients. R0-resection was possible in all cases, although there was a perirectal tumor infiltration to less than 2 mm to circumference of the surgical specimen in 2 cases and unexpected small liver metastasis in 5 cases. Complete remission rate was 23.3% (10 cases). Detecting small amounts of vital tumor cells in altered tissue after chemoradiotherapy is a major problem of pathological examination procedure and should be taken into consideration by the surgeons. The choice of operation (resection vs. abdominoperineal extirpation vs. local excision) should be committed to the initial imaging procedure and not to any restaging procedure after neoadjuvant chemoradiotherap

Current controversies in radiotherapy for breast cancer

Multimodal treatment approaches have substantially improved the outcome of breast cancer patients in the last decades. Radiotherapy is an integral component of multimodal treatment concepts used in curative and palliative intention in numerous clinical situations from precursor lesions such as ductal carcinoma in situ (DCIS) to advanced breast cancer. This review addresses current controversial topics in radiotherapy with special consideration of DCIS, accelerated partial breast irradiation (APBI) and regional nodal irradiation (RNI) and provides an update on the clinical practice guidelines of the Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO)

Genetic predictors of acute toxicities related to radiation therapy following lumpectomy for breast cancer: a case-series study

INTRODUCTION: The cytotoxic effects of radiation therapy are mediated primarily through increased formation of hydroxyl radicals and reactive oxygen species, which can damage cells, proteins and DNA; the glutathione S-transferases (GSTs) function to protect against oxidative stress. We hypothesized that polymorphisms encoding reduced or absent activity in the GSTs might result in greater risk for radiation-associated toxicity. METHODS: Women receiving therapy in radiation units in Germany following lumpectomy for breast cancer (1998–2001) provided a blood sample and completed an epidemiological questionnaire (n = 446). Genotypes were determined using Sequonom MALDI-TOF (GSTA1, GSTP1) and Masscode (GSTM1, GSTT1). Biologically effective radiotherapy dose (BED) was calculated, accounting for differences in fractionation and overall treatment time. Side effects considered were grade 2c and above, as classified using the modified Common Toxicity Criteria. Predictors of toxicity were modelled using Cox regression models in relation to BED, with adjustment for treating clinic, photon field, beam energy and boost method, and potential confounding variables. RESULTS: Low activity GSTP1 genotypes were associated with a greater than twofold increase in risk for acute skin toxicities (adjusted hazard ratio 2.28, 95% confidence interval 1.04–4.99). No associations were noted for the other GST genotypes. CONCLUSION: These data indicate that GSTP1 plays an important role in protecting normal cells from damage associated with radiation therapy. Studies examining the effects of GSTP1 polymorphisms on toxicity, recurrence and survival will further inform individualized therapeutics based on genotypes

Romancing the Boost – the Higher, the Better?

In terms of radiobiology, the probability of tumor control is essentially a function of dose, with a direct (sigmoid) correlation,predominantly irrespective of the cancer type. In practice, the ability to deliver ultimately tumoricidal doses is frequently limited by the tolerance of surrounding organs at risk for radiation damage,especially when microscopic spread involves critical amounts of radiosensitive tissues. Permanent local tumor control, however, is one of the prerequisites for definitive cure from cancer: the higher the rate of local control, the lower the risk of subsequent systemic spread with consecutive death from disease. As early as 1997, Sam Hellman was the first to summarize this thesis in an extremely concise phrase: to ‘stop metastases at their source’ [1]