Survey of current practices from an international task force for gynecological stereotactic ablative radiotherapy.

BACKGROUND: Stereotactic Ablative Radiotherapy (SABR) is an effective treatment that improves local control for many tumours. However, the role of SABR in gynecological cancers (GYN) has not been well-established. We hypothesize that there exists considerable variation in GYN-SABR practice and technique. The goal of this study is to describe clinical and technical factors in utilization of GYN-SABR among 11 experienced radiation oncologists. MATERIALS AND METHODS: A 63 question survey on GYN-SABR was sent to 11 radiation oncologists (5 countries) who have published original research, conducted trials or have an established program at their institutions. Responses were combined and analyzed at a central institution. RESULTS: Most respondents indicated that salvage therapy (non-irradiated or re-irradiated field) for nodal (81%) and primary recurrent disease (91%) could be considered standard options for SABR in the setting of inability to administer brachytherapy. All other indications should be considered on clinical trials. Most would not offer SABR as a boost in primary treatment off-trial without absolute contraindications to brachytherapy. Multi-modality imaging is often (91%) used for planning including PET, CT contrast and MRI. There is a wide variation for OAR tolerances however small bowel is considered the dose-limiting structure for most experts (91%). Fractionation schedules range from 3 to 6 fractions for nodal/primary definitive and boost SABR. CONCLUSIONS: Although SABR has become increasingly standard in other oncology disease sites, there remains a wide variation in both clinical and technical factors when treating GYN cancers. Nodal and recurrent disease is considered a potential indication for SABR whereas other indications should be offered on clinical trials. This study summarizes SABR practices among GYN radiation oncologists while further studies are needed to establish consensus guidelines for GYN-SABR treatment.

The European study on centralisation of childhood cancer treatment.

BACKGROUND: It is generally agreed to centralise treatment of childhood cancers (CCs). We analysed (1) the degree of centralisation of CCs in European countries and 2) the relations between centralisation and survival. PATIENTS AND METHODS: The analysis comprised 4415 CCs, diagnosed between 2000 and 2007 and followed up to the end of 2013, from Belgium, Bulgaria, Finland, Ireland, the Netherlands and Slovenia. All these countries had national population-based cancer registries and were able to provide information on diagnosis, treatment, treatment hospitals, and survival. Each case was then classified according to whether the patient was treated in a high- or a low-volume hospital among those providing CC treatment. A Cox proportional hazard model was used to calculate the relation between volume category and five-year survival, adjusting by age, sex and diagnostic group. RESULTS: The number of hospitals providing treatment for CCs ranged from six (Slovenia) to slightly more than 40 (the Netherlands and Belgium). We identified a single higher volume hospital in Ireland and in Slovenia, treating 80% and 97% of cases, respectively, and three to five major hospitals in the other countries, treating between 65% and 93% of cases. Outcome was significantly better when primary treatment was given in high-volume hospitals compared to low-volume hospitals for central nervous system tumours (relative risk [RR] = 0.71), haematologic tumours (RR = 0.74) and for all CC combined (RR = 0.83). CONCLUSION: Treatment centralisation is associated with survival benefits and should be further strengthened in these countries. New plans for centralisation should include ongoing evaluation.

Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study.

PURPOSE: Discordances between the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), expression between primary breast tumors and their subsequent brain metastases (BM) were investigated in breast cancer patients. METHODS: We collected retrospective data from 11 institutions in 8 countries in a predefined-standardized format. Receptor status (positive or negative) was determined according to institutional guidelines (immunohistochemically and/or fluorescence in situ hybridization). The study was subject to each institution's ethical research committee. RESULTS: A total of 167 breast cancer patients with BM were included. 25 patients out of 129 with a complete receptor information from both primary tumor and BM (ER, PR, HER2) available, had a change in receptor status: 7 of 26 (27%) ER/PR-positive/HER2-negative primaries (3 gained HER2; 4 lost expression of ER/PR); 10 of 31 (32%) ER/PR-positive/HER2-positive primaries (4 lost ER/PR only; 3 lost HER2 only; 3 lost both ER/PR and HER2); one of 33 (3%) ER/PR-negative receptor/HER2-positive primaries (gained ER); and 7 of 39 (18%) triple-negative primaries (5 gained ER/PR and 2 gained HER2). CONCLUSIONS: The majority of breast cancer patients with BM in this series had primary HER2-enriched tumors, followed by those with a triple-negative profile. One out of 5 patients had a receptor discrepancy between the primary tumor and subsequent BM. Therefore, we advise receptor status assessment of BM in all breast cancer patients with available histology as it may have significant implications for therapy.

Influence of enteral glutamine on inflammatory and hormonal response in patients with rectal cancer during preoperative radiochemotherapy.

We conducted a randomized double-blind placebo-controlled study evaluating the influence of 5 weeks' duration of 30 g enteral glutamine supplementation on inflammatory and hormonal responses in 73 patients with rectal cancer undergoing preoperative radiochemotherapy. Plasma levels of inflammatory and hormonal parameters were controlled at the beginning and at the end of supplementation. Enteral glutamine resulted in modulation of inflammatory and hormonal responses as shown by a decreased plasma interleukin 6 and cortisol levels in glutamine compared with placebo group: 5.5±3.8 versus 11.1±19.9 ng/l (P=0.02) for IL-6 and 386±168.4 to 312.7±111.7 nmol/l (P=0.03) for cortisol. We conclude that enteral glutamine exhibits some anti-inflammatory activity and, consequently, leads to a lower hormonal stress response during radiochemotherapy in patients with rectal cancer.

Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves.

Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the brain, brainstem, cavernous sinus, and optic apparatus and the resulting complex geometry. Surgical resection caries a high risk of morbidity and is often not an option for these patients. Stereotactic radiosurgery and radiotherapy are potential treatment options for patients with cancer involving the trigeminal or facial nerve. These techniques can deliver high doses of radiation to complex volumes while sparing adjacent critical structures. In the current study, seven cases of cancer involving the trigeminal or facial nerve are presented. These patients had unresectable recurrent or residual disease after definitive local therapy. Each patient was treated with stereotactic radiation therapy using a linear accelerator based system. A multidisciplinary approach including neuroradiology and surgical oncology was used to delineate target volumes. Treatment was well tolerated with no acute grade 3 or higher toxicity. One patient who was reirradiated experienced cerebral radionecrosis with mild symptoms. Four of the seven patients treated had no evidence of disease after a median follow up of 12 months (range 2-24 months). A dosimetric analysis was performed to compare intensity modulated fractionated stereotactic radiation therapy (IM-FSRT) to a 3D conformal technique. The dose to 90% (D90) of the brainstem was lower with the IM-FSRT plan by a mean of 13.5 Gy. The D95 to the ipsilateral optic nerve was also reduced with IM-FSRT by 12.2 Gy and the D95 for the optic chiasm was lower with FSRT by 16.3 Gy. Treatment of malignancies involving a cranial nerve requires a multidisciplinary approach. Use of an IM-FSRT technique with a micro-multileaf collimator resulted in a lower dose to the brainstem, optic nerves and chiasm for each case examined.

Multivariate analysis of electrical impedance spectra for relaxed and contracted skeletal muscle.

Four-electrode impedance spectra of relaxed and contracted muscle biceps brachii were analyzed in an adult human subject over the frequency range from 300 Hz to 75 kHz. A feasibility of the principal component analysis of bioimpedance measurement for the evaluation of skeletal muscle contractile state was examined. The principal components score plots show a data grouping of the impedance spectra from the two muscle groups. The classification was performed using a soft independent modeling of class analogy (SIMCA) method. The data set comprised 32 samples (16 samples of contracted muscle and 16 samples of relaxed muscle). The leave-one-out test of the classification yields about 80% of correctly classified samples (11 samples for contracted and 15 samples for relaxed muscle).

An instrumentation amplifier as a front-end for a four-electrode bioimpedance measurement.

The performance of a monolithic instrumentation amplifier used as an interface for a four-electrode bioimpedance measurement is examined with a commercially available impedance meter based on an auto-balancing bridge. The errors due to particularities in the input stage of the impedance meter, when used without a front-end, were several orders of magnitude higher than the measured quantity. The analysis was performed on an electrical circuit model of the skin and electrodes over a frequency range of 20 Hz to 1 MHz. The achieved accuracy with balanced electrode impedances for the frequencies up to 100 kHz can be below 0.2% for impedance magnitude and 0.1 degrees for impedance phase, which is within the specified basic accuracy range of the LCR-meter used for the measurements. At frequencies above 100 kHz the errors are increasing and are higher than the LCR-meter's basic accuracy. This study indicates that use of an instrumentation amplifier as a front-end with the particular LCR-meter can significantly improve the measurement accuracy of the four-electrode bioimpedance measurement at low frequencies.

Verrucous carcinoma of the larynx: determining the best treatment option.

BACKGROUND: Verrucous carcinoma (VC) of the larynx is a rare variant of well-differentiated squamous cell carcinoma, characterized by locally invasive, exophytic warty growth. The purpose of the present study was to evaluate the experience with this rare disease in Slovenia over a 23-year period and to weigh the potential for cure of different treatment options against the functional outcome. MATERIALS AND METHODS: The databases of the Cancer Registry of Slovenia as well as of the registries of all three departments licensed for the treatment of laryngeal cancer in the country were used for the identification of patients. Presentation, diagnosis, treatment and outcome were reviewed retrospectively. RESULTS: From 1980 to 2002, 30 patients were diagnosed with VC of the larynx, representing 1.23% of all laryngeal malignancies. The most frequent site of origin was the glottis. Twenty-three patients had surgery (functional 13; total laryngectomy 10), three patients had radiotherapy, and a combination of irradiation and concomitant chemotherapy was used in four patients. Only one tumor recurred, six months after primary radiation treatment, but was successfully salvaged with a total laryngectomy. The 5-year overall survival rate of 75% was not significantly different from an age- and sex-matched cohort from the Slovenian population (P=0.071). CONCLUSIONS: In VC of the larynx, determination of treatment options should be dictated by voice preservation strategies. Surgery remains the gold standard of treatment. However, concomitant radiochemotherapy emerges as an attractive alternative to mutilating surgical procedures.

Validation of an accelerometer for determination of muscle belly radial displacement.

A commercial variable-capacitance micromachined accelerometer was validated for muscle belly radial displacement measurement. The displacement was calculated by the acceleration data being integrated twice and was compared with the results obtained simultaneously by an accurate mechanical displacement sensor based on an optical encoder. The aim of the investigation was to evaluate the accuracy and precision of an accelerometer for tensiomyography, which is a method for the detection of skeletal muscle contractile properties on the basis of muscle belly radial displacement. A hundred measurements at a bandwidth of 2300 Hz were performed. It was shown that the accuracy and precision in determination of the maximum displacement and the time of the maximum displacement from the calculated curve were satisfactory, in spite of the standard deviation of the twice-integrated acceleration growing approximately linearly with time. The results were accurate enough since the elapsed time from the beginning of the integration was small (less than 75 ms). The measured maximum displacement ranges were between 9.2 and 10.2 mm. The mean relative error was less than 1% (SD = 0.02mm) for the maximum displacement and about 1% (SD = 0.6 ms) for the time to maximum displacement. The accuracy of the half-relaxation time determination was more uncertain because of the relatively high relative error of -2.4% (SD = 3 ms). Results showed that a commercial micromachined accelerometer could be suitable for the measurement of muscle belly radial displacement and used for development of a future miniaturised and flexible system for the measurement of similar displacements.