Concurrent radiochemotherapy (RCT) is a promising new therapy option in advanced non-small cell lung cancer (NSCLC). In randomized trials concomitant RCT has been shown to be superior compared to ...radiotherapy alone and to sequential radiochemotherapy. In most treatment schedules platinum salts alone or in combination with etoposide, mitomycin C or vinca-alkaloids have been used. Up to now altered fractionation schemas—particularly hyperfractionated radiotherapy—have not been demonstrated to be superior to conventional fractionation (2 Gy daily up to 56–60 Gy), when employed concurrently to chemotherapy. Nevertheless open questions remain: (1) What is the best chemotherapy administered simultaneously to radiotherapy? (2) Might newer drugs (e.g. taxanes, inhibitors of topoisomerase I and II, gemcitabine) be more effective and reveal fewer side effects compared to platinum salts? (3) Is there a role for adjuvant chemotherapy following RCT? (4) What is the most effective radiotherapy schedule in concepts with RCT? (5) What radiation dose is necessary to optimize local control in RCT?
Joint application of standard tumor therapies like radiotherapy and/or chemotherapy with immune therapy has long been considered not to fit. However, it has become accepted that immune responses may ...contribute to the elimination of cancer cells. We present how in vivo–induced tumor cell death by irradiation, chemotherapeutic agents, or hyperthermia can be rendered more immunogenic. High hydrostatic pressure is introduced as an innovative inactivation method for tumor cells used as vaccines. Annexin A5, being a natural occurring ligand for phosphatidylserine that is exposed by dying tumor cells, renders apoptotic tumor cells immunogenic and induces tumor regression. Combinations of irradiation with hyperthermia may also foster antitumor responses. For preparation of autologous tumor cell vaccines, high hydrostatic pressure is suitable to induce immunogenic cancer cell death. Future work will be aimed toward evaluating which combination and chronological sequence of radiotherapy, chemotherapy, hyperthermia, annexin A5, and/or autologous tumor cell vaccines will induce specific and long‐lasting antitumor immunity.
Background
Tumor board recommendations for breast cancer are mainly based on patient characteristics and prognostic tumor parameters. In the era of potential avoidance of axillary surgery we evaluate ...the impact of pathologic nodal status for adjuvant treatment decisions.
Methods
Postoperative tumor board records of 207 patients over a 1-year period were rediscussed without knowledge of pathologic nodal status. Differences were classified as major (chemotherapy and/or radiotherapy: present/absent) or minor (different chemotherapeutic protocols) discrepancies. The survival rates among subgroups were calculated using Adjuvant! Online tool.
Results
The tumor board without information of pathologic nodal status resulted in treatment changes in 72 of the 207 patients studied (34.8%). Major discrepancies were observed in 37 patients (17.9%). The survival rates were not significantly different due to a balanced overtreatment and undertreatment in this subgroup. Lymphovascular invasion (LVI) was an independent parameter used to predict the subgroup with major discrepancies (
P
= .001; RR = 4.9 95% CI, 1.9–12.7).
Conclusions
The knowledge of pathologic nodal status is important for postoperative chemotherapy and postmastectomy radiotherapy indications. There is a risk for one-third of all patients when avoiding axillary surgery to get an adjuvant therapy that differs from the current guidelines especially in carcinomas with present LVI.
Traditionally, the decision to apply preoperative treatment for rectal cancer patients has been based on the T- and N-category. Recently, the radial distance of the tumor to the circumferential ...resection margin (CRM) has been identified as an important risk factor for local failure. By magnetic resonance imaging (MRI) this distance can be measured preoperatively with high reliability. Thus, selected groups have started to limit the indication for preoperative therapy to tumors extending to - or growing within 1 mm from - the mesorectal fascia (CRM+).
Pros and cons of this selected approach for preoperative treatment and first clinical results are presented. Prerequisites are the availability of modern high-resolution thin-section MRI technology as well as strict quality control of MRI and surgical quality of total mesorectal excision (TME).
By selecting patients with CRM-positive tumors on MRI for preoperative therapy, only approximately 35% patients will require preoperative radiotherapy (RT) or radiochemotherapy (RCT). However, with histopathologic work-up of the resected specimen after primary surgery, the indication for postoperative RCT is given for a rather large percentage of patients, i.e., for pCRM+ (5-10%), intramesorectal or intramural excision (30-40%), pN+ (30-40%). Postoperative RCT, however, is significantly less effective and more toxic than preoperative RCT. A further point of concern is the assertion that patients, in whom a CRM-negative status is achieved by surgery alone, do not benefit from additional RT. Data of the Dutch TME trial and the British MRC (Medical Research Council) CR07 trial, however, suggest the reverse.
To omit preoperative RT/RCT for CRM-negative tumors on MRI needs to be further investigated in prospective clinical trials. The German guidelines for the treatment of colorectal cancer 2008 continue to indicate preoperative RT/RCT based on the T- and N-category.
Promyelocytic leukemia nuclear bodies (PML-NBs) have been depicted as structures which are involved in processing cell damages and DNA double-strand break repairs. The study was designed to evaluate ...differences in patients' PML-NBs response to stress factors like a cancerous disease and ionizing radiation exposure dependent on age.
In order to clarify the role of PML-NBs in the aging process, we examined peripheral blood monocytes of 134 cancer patients and 41 healthy individuals between 22 and 92 years of age, both before and after in vitro irradiation. Additionally, we analyzed the samples of the cancer patients after in vivo irradiation. Cells were immunostained and about 1600 cells per individual were analyzed for the presence of PML- and γH2AX foci.
The number of existing PML-NBs per nucleus declined with age, while the number of γH2AX foci increased with age. There was a non-significant trend that in vivo irradiation increased the number of PML-NBs in cells of young study participants, while in older individuals PML-NBs tended to decrease. It can be assumed that PML-NBs decrease in number during the process of aging.
The findings suggest that there is a dysfunctional PML-NBs stress response in aged cells.
Objective
Patients with systemic lupus erythematosus (SLE) are often characterized by cellular as well as humoral deficiencies in the recognition and phagocytosis of dead and dying cells. The aim of ...this study was to investigate whether the remnants of apoptotic cells are involved in the induction of inflammatory cytokines in blood‐borne phagocytes.
Methods
We used ex vivo phagocytosis assays comprising cellular and humoral components and phagocytosis assays with isolated granulocytes and monocytes to study the phagocytosis of secondarily necrotic cell–derived material (SNEC). Cytokines were measured by multiplex bead array technology.
Results
We confirmed the impaired uptake of various particulate targets, including immunoglobulin‐opsonized beads, by granulocytes and monocytes from patients with SLE compared with healthy control subjects. Surprisingly, blood‐borne phagocytes from two‐thirds of the patients with SLE took up SNEC, which was rarely phagocytosed by phagocytes from healthy control subjects or patients with rheumatoid arthritis. Supplementation of healthy donor blood with IgG fractions derived from patients with SLE transferred the capability to take up SNEC to the phagocytes of healthy donors. Phagocytosis‐promoting immune globulins also induced secretion of huge amounts of cytokines by blood‐borne phagocytes following uptake of SNEC.
Conclusion
Opsonization of SNEC by autoantibodies from patients with SLE fosters its uptake by blood‐borne monocytes and granulocytes. Autoantibody‐mediated phagocytosis of SNEC is accompanied by secretion of inflammatory cytokines, fueling the inflammation that contributes to the perpetuation of autoimmunity in SLE.
Purpose:To investigate radiation oncologists’ opinions on important considerations to offering re-irradiation (re-RT) as a treatment option for recurrent glioma.Materials and methods:A survey was ...conducted with 13 radiation oncologists involved in the care of central nervous system tumor patients. The survey was comprised of 49 questions divided into 2 domains: a demographic section (10 questions) and a case section (5 re-RT cases with 5 to 6 questions representing one or several re-RT treatment dilemmas as may be encountered in the clinic). Respondents were asked to rate the relevance of various factors to offering re-RT, respond to the cases with a decision to offer re-RT vs. not, volume to be treated, margins to be employed, dose/fractionation suggested and any additional comments with respect to rationale in each scenario.Results:Sixty nine percent of responders have been practicing for greater than 10 years and 61% have re-RT 20 to 100 patients to date, with 54% seeing 2–5 re-RT cases per month and retreating 1–2 patients per month. Recurrent tumor volume, time since previous radiation therapy, previously administered dose to organs at risk and patient performance status were rated by the majority of responders (85%, 92%, 77%, and 69% respectively) as extremely relevant or very relevant to offering re-RT as an option.Conclusion:The experts’ practice of re-RT is still heterogeneous, reflecting the paucity of high-quality prospective data available for decision-making. Nevertheless, practicing radiation oncologists can support own decisions by referring to the cases found suitable for re-RT in this survey.
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