Suboccipital lateral injection of intrathecal chemotherapy in a patient with mantle cell lymphoma

Background: Even today patients who suffer from mantle cell lymphoma have a poor prognosis, especially when the CNS is involved. To confirm the diagnosis of meningeosis lymphomatosa, asservation of the liquor cerebrospinalis is necessary. During this procedure, intrathecal chemotherapy may be given if there is clinical evidence of meningeosis. If lumbar puncture cannot be performed, a lateral suboccipital puncture may be an alternative approach. Patient and Methods: We report the case of a 65-year-old patient who suffered from mantle cell lymphoma stage IV. The patient presented with symptoms of progressive paraparesis of both legs and incontinence, with tumor mass intradural from the 12th thoracic vertebra to the level of S1. During irradiation, the patient developed symptoms of diffuse meningiosis lymphomatosa. The conventional lumbar puncture was impossible, because of tumor present in the thoracico-lumbar junction. Results: A suboccipital puncture was performed for both collecting cerebrospinal fluid and application of chemotherapy ( cytosine arabinoside/dexamethasone). This lead to remarkable improvement of the patient's clinical symptoms. Conclusion: The suboccipital cervical puncture was performed without complications. A variation of the intrathecal approach is described, which may serve as alternative when conventional lumbar puncture is not possible

Feasibility and morbidity of combined hyperthermia and radiochemotherapy in recurrent rectal cancer - Preliminary results

Background: The local recurrence rate of colorectal cancer has been significantly reduced due to the use of combined radiochemotherapy. Despite this improvement regarding locally advanced tumour recurrences, the treatment strategy for pre-treated patients remains difficult and unresolved. Patients and Methods: We analysed treatment and follow-up data of 14 patients with local recurrence of rectal cancer who were treated with radiation therapy (RT), chemotherapy (CT) and regional hyperthermia (RHT) from November 1997 to December 2001. Nine of these patients had received irradiation and CT (=pre-treated patients) in the past. For this group, 30.6-39.6 Gy RT, 5-fluorouracil (5-FU) as a continuous infusion over 5 days per week (350 mg/m(2)/24 h) combined with RHT twice a week was given. The 5 remaining patients (=not pre-treated) received conformal irradiation of 45 Gy with a boost between 9 and 14.4 Gy, combined with continuous infusion of 5-FU on days 1-4, and 29-33 (500 mg/m(2)/24 h), and RHT twice a week. Response to therapy was evaluated by means of computed tomography (CT) or magnetic resonance imaging (MRI) and by clinical follow-up. Results: Among 13 evaluated cases, the overall objective response rate was 54% (5 complete responses, 2 partial responses). At mean follow-up of 13.9 months (range 5-32 months) 7 patients were alive. Conclusion: The therapeutic regimen appears to be active in the treatment of local recurrences of rectal cancer. Larger-scaled studies are needed to evaluate the potency of hyperthermia in this therapeutic strategy

Quantification of the response of circulating epithelial cells to neodadjuvant treatment for breast cancer: a new tool for therapy monitoring

INTRODUCTION: In adjuvant treatment for breast cancer there is no tool available with which to measure the efficacy of the therapy. In contrast, in neoadjuvant therapy reduction in tumour size is used as an indicator of the sensitivity of tumour cells to the agents applied. If circulating epithelial (tumour) cells can be shown to react to therapy in the same way as the primary tumour, then this response may be exploited to monitor the effect of therapy in the adjuvant setting. METHOD: We used MAINTRAC(® )analysis to monitor the reduction in circulating epithelial cells during the first three to four cycles of neoadjuvant therapy in 30 breast cancer patients. RESULTS: MAINTRAC(® )analysis revealed a patient-specific response. Comparison of this response with the decline in size of the primary tumour showed that the reduction in number of circulating epithelial cells accurately predicted final tumour reduction at surgery if the entire neoadjuvant regimen consisted of chemotherapy. However, the response of the circulating tumour cells was unable to predict the response to additional antibody therapy. CONCLUSION: The response of circulating epithelial cells faithfully reflects the response of the whole tumour to adjuvant therapy, indicating that these cells may be considered part of the tumour and can be used for therapy monitoring

Suboccipital lateral injection of intrathecal chemotherapy in a patient with mantle cell lymphoma

Background: Even today patients who suffer from mantle cell lymphoma have a poor prognosis, especially when the CNS is involved. To confirm the diagnosis of meningeosis lymphomatosa, asservation of the liquor cerebrospinalis is necessary. During this procedure, intrathecal chemotherapy may be given if there is clinical evidence of meningeosis. If lumbar puncture cannot be performed, a lateral suboccipital puncture may be an alternative approach. Patient and Methods: We report the case of a 65-year-old patient who suffered from mantle cell lymphoma stage IV. The patient presented with symptoms of progressive paraparesis of both legs and incontinence, with tumor mass intradural from the 12th thoracic vertebra to the level of S1. During irradiation, the patient developed symptoms of diffuse meningiosis lymphomatosa. The conventional lumbar puncture was impossible, because of tumor present in the thoracico-lumbar junction. Results: A suboccipital puncture was performed for both collecting cerebrospinal fluid and application of chemotherapy ( cytosine arabinoside/dexamethasone). This lead to remarkable improvement of the patient's clinical symptoms. Conclusion: The suboccipital cervical puncture was performed without complications. A variation of the intrathecal approach is described, which may serve as alternative when conventional lumbar puncture is not possible

Promising development from translational or perhaps anti-translational research in breast cancer

Background: A great deal of the public’s money has been spent on cancer research but demonstrable benefits to patients have not been proportionate. We are a group of scientists and physicians who several decades ago were confronted with bimodal relapse patterns among early stage breast cancer patients who were treated by mastectomy. Since the bimodal pattern was not explainable with the then well-accepted continuous growth model, we proposed that metastatic disease was mostly inactive before surgery but was driven into growth somehow by surgery. Most relapses in breast cancer would fall into the surgery-induced growth category thus it was highly important to understand the ramifications of this process and how it may be curtailed. With this hypothesis, we have been able to explain a wide variety of clinical observations including why mammography is less effective for women age 40–49 than it is for women age 50–59, why adjuvant chemotherapy is most effective for premenopausal women with positive lymph nodes, and why there is a racial disparity in outcome. Methods: We have been diligently looking for new clinical or laboratory information that could provide a connection or correlation between the bimodal relapse pattern and some clinical factor or interventional action and perhaps lead us towards methods to prevent surgery-initiated tumor activity. Results: A recent development occurred when a retrospective study appeared in an anesthesiology journal that suggested the perioperative NSAID analgesic ketorolac seems to reduce early relapses following mastectomy. Collaborating with these anesthesiologists to understand this effect, we independently re-examined and updated their data and, in search of a mechanism, focused in on the transient systemic inflammation that follows surgery to remove a primary tumor. We have arrived at several possible explanations ranging from mechanical to biological that suggest the relapses avoided in the early years do not show up later. Conclusions: We present the possibility that a nontoxic and low cost intervention could prevent early relapses. It may be that preventing systemic inflammation post surgery will prevent early relapses. This could be controlled by the surgical anesthesiologist’s choice of analgesic drugs. This development needs to be confirmed in a randomized controlled clinical trial and we have identified triple negative breast cancer as the ideal subset with which to test this. If successful, this would be relatively easy to implement in developing as well as developed countries and would be an important translational result

NSAID analgesic ketorolac used perioperatively may suppress early breast cancer relapse: particular relevance to triple negative subgroup

To explain a bimodal relapse hazard among early stage breast cancer patients treated by mastectomy we postulated that relapses within 4 years of surgery resulted from something that happened at about the time of surgery to provoke sudden exits from dormant phases to active growth. Relapses at 10 months appeared to be surgery-induced angiogenesis of dormant avascular micrometastases. Another relapse mode with peak about 30 months corresponded to sudden growth from a single cell. Late relapses were not synchronized to surgery. This hypothesis could explain a wide variety of breast cancer observations. We have been looking for new data that might provide more insight concerning the various relapse modes. Retrospective data reported in June 2010 study of 327 consecutive patients compared various perioperative analgesics and anesthetics in one Belgian hospital and one surgeon. Patients were treated with mastectomy and conventional adjuvant therapy. Follow-up was average 27.3 months with range 13–44 months. Updated hazard as of September 2011 for this series is now presented. NSAID ketorolac, a common analgesic used in surgery, is associated with far superior disease-free survival in the first few years after surgery. The expected prominent early relapse events are all but absent. In the 9–18 month period, there is fivefold reduction in relapses. If this observation holds up to further scrutiny, it could mean that the simple use of this safe and effective anti-inflammatory agent at surgery might eliminate most early relapses. Transient systemic inflammation accompanying surgery could be part of the metastatic tumor seeding process and could have been effectively blocked by perioperative anti-inflammatory agents. In addition, antiangiogenic properties of NSAIDs could also play a role. Triple negative breast cancer may be the ideal group with which to test perioperative ketorolac to prevent early relapses

Circulating tumor cells in blood of primary breast cancer patients assessed by a novel RT-PCR test kit and comparison with status of bone marrow-disseminated tumor cells

In breast cancer, circulating tumor cells (CTCs)/disseminated tumor cells (DTCs) may serve as independent adverse prognostic variables, to monitor the course of the disease and to predict response or failure to cancer therapy. Most of the techniques to enumerate DTCs in the bone marrow or CTCs in the bloodstream of breast cancer patients rely on a combination of an enrichment step and a detection step. A novel RT-PCR method, the AdnaTest BreastCancer™ kit, was developed for the enrichment of CTCs from peripheral blood of breast cancer patients followed by identification of CTC-associated marker transcripts by reverse transcription and PCR. Although this test has been demonstrated to identify breast cancer patients at risk, standardization of this technique and direct comparison with other established breast cancer CTC enrichment and detection techniques is still lacking, but highly needed. This is done best within prospective clinical trials, such as in the ongoing DETECT, SUCCESS, and BR-01-2004 trials

Interobserver agreement on definition of the target volume in stereotactic radiotherapy for pancreatic adenocarcinoma using different imaging modalities

PURPOSE The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes. METHODS Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS). RESULTS For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression. CONCLUSION Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA

Recent translational research: circulating tumor cells in breast cancer patients

In breast cancer patients, hematogenous tumor cell dissemination can be detected, even at the single cell level, by applying immunocytochemical and molecular assays. Various methods for the detection of circulating tumor cells in the peripheral blood have been described. Results from recently reported studies suggest that circulating tumor cell levels may serve as a prognostic marker and for the early assessment of therapeutic response in patients with metastatic breast cancer. However, in early-stage breast cancer, the impact of circulating tumor cells is less well established than the presence of disseminated tumor cells in bone marrow; several clinical studies have demonstrated that cells of the latter type are an independent prognostic factor at primary diagnosis. In this article we briefly summarize recent studies examining the presence of circulating tumor cells in the blood and discuss further clinical applications