No abstract

A dose gradient index (GI) is proposed that can be used to compare treatment plans of equal conformity. The steep dose gradient outside the radiosurgical target is one of the factors that makes radiosurgery possible. It therefore makes sense to measure this variable and to use it to compare rival plans, explore optimal prescription isodoses, or compare treatment modalities.The GI is defined as the ratio of the volume of half the prescription isodose to the volume of the prescription isodose. For a plan normalized to the 50% isodose line, it is the ratio of the 25% isodose volume to that of the 50% isodose volume.The GI will differentiate between plans of similar conformity, but with different dose gradients, for example, where isocenters have been inappropriately centered on the edge of the target volume.In a retrospective series of 50 dose plans for the treatment of vestibular schwannoma, the optimal prescription isodose was assessed. A mean value of 40% (median 38%, range 30-61%) was calculated, not 50% as might be anticipated. The GI can show which of these prescription isodoses will give the steepest dose falloff outside the target.When planning a multiisocenter treatment, there may be a temptation to place some isocenters on the edge of the target. This has the apparent advantage of producing a plan of good conformity and a predictable prescription isodose; however, it risks creating a plan that has a low dose gradient outside the target. The quality of this dose gradient is quantified by the GI.KEY WORDS r Gamma Knife surgery r dose planning r radiosurgery r conformity r selectivity r dose gradient Address reprint requests to: Ian Paddick, M.Sc.,

Objective: In tumor patients, IL-6 appears to be one component of a consistent cancer-associated cytokine network resulting in both a systemic immune stimulation and a microenvironment of cancer-induced immune suppression that ultimately protects the cancer cells. IL-6 has been associated with prognosis in cancer patients, but so far a systemical analysis has not been carried out. Methods: The present meta-analysis studies the relation between IL-6 serum levels and the prognosis of cancer patients in the available clinical literature of 100 articles published between 1993 and 2013 comprising 11,583 patients. Results: The IL-6 serum level was described as significantly correlating with survival in 82/101 series comprising 85.6% of patients (9917/11,583) with 23 different cancer types. A total of 64 studies dichotomized patient cohorts according to various cut-off IL-6 serum levels: in 59/64 of these series corresponding to 94.5% of the reported patients (7694/8142) significant correlations between IL-6 serum level and survival were seen. The median survival of cancer patients had been determined above various cut-off levels of serum IL-6 in 24 dichotomized studies (26 cohorts). There was a highly significant inverse correlation between median survival of the cohorts with IL-6 serum level above cut-off (1272 patients) and their corresponding IL-6 cut-off values (Spearman R -0,48 p= < 0.001) following a linear regression when both parameters were log-transformed (p < 0.001). A significant correlation between increasing serum IL-6 and tumor stage or metastases was described in 39/44 studies and 91% of published patients (4221/4636) where clinical parameters had been specified. Conclusions: Closely associated with the patient's clinical condition and independent of the cancer histology, the increased IL-6 serum level uniformly appears to correlate with survival as paraneoplastic condition in later cancer stages independent of the cancer type. Modifications of this paraneoplastic immune reaction may offer new therapeutic options in cancer.

Chemotherapy has made substantial progress in the therapy of systemic cancer, but the pharmacological efficacy is insufficient in the treatment of brain metastases. Fractionated whole brain radiotherapy (WBRT) has been a standard treatment of brain metastases, but provides limited local tumor control and often unsatisfactory clinical results. Stereotactic radiosurgery using Gamma Knife, Linac or Cyberknife has overcome several of these limitations, which has influenced recent treatment recommendations. This present review summarizes the current literature of single session radiosurgery concerning survival and quality of life, specific responses, tumor volumes and numbers, about potential treatment combinations and radioresistant metastases. Gamma Knife and Linac based radiosurgery provide consistent results with a reproducible local tumor control in both single and multiple brain metastases. Ideally minimum doses of ≥18Gy are applied. Reported local control rates were 90-94% for breast cancer metastases and 81-98% for brain metastases of lung cancer. Local tumor control rates after radiosurgery of otherwise radioresistant brain metastases were 73-90% for melanoma and 83-96% for renal cell cancer. Currently, there is a tendency to treat a larger number of brain metastases in a single radiosurgical session, since numerous studies document high local tumor control after radiosurgical treatment of >3 brain metastases. New remote brain metastases are reported in 33-42% after WBRT and in 39-52% after radiosurgery, but while WBRT is generally applied only once, radiosurgery can be used repeatedly for remote recurrences or new metastases after WBRT. Larger metastases (>8-10cc) should be removed surgically, but for smaller metastases Gamma Knife radiosurgery appears to be equally effective as surgical tumor resection (level I evidence). Radiosurgery avoids the impairments in cognition and quality of life that can be a consequence of WBRT (level I evidence). High local efficacy, preservation of cerebral functions, short hospitalization and the option to continue a systemic chemotherapy are factors in favor of a minimally invasive approach with stereotactic radiosurgery.