Use of EORTC Target Definition Guidelines for Dose-Intensified Salvage Radiation Therapy for Recurrent Prostate Cancer: Results of the Quality Assurance Program of the Randomized Trial SAKK 09/10

PURPOSE Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice. METHODS AND MATERIALS A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared. RESULTS Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm(3)), and decrease in the union volume (79.3 vs 84.2 cm(3)). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different. CONCLUSIONS The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.

Ankle dorsiflexion arthrodesis to salvage Chopart's amputation with anterior skin insufficiency

BACKGROUND In Chopart-level amputations the heel often deviates into equinus and varus when, due to the lack of healthy anterior soft tissue, rebalancing tendon transfers to the talar head are not possible. Consequently, anterior and lateral wound dehiscence and ulceration may occur requiring higher-level amputation to achieve wound closure, with considerable loss of function for the patients. METHODS Twenty-four consecutive patients (15 diabetes, 6 trauma, and 3 tumor) had Chopart's amputation and simultaneous or delayed additional ankle dorsiflexion arthrodesis to allow for tension-free wound closure or soft tissue reconstruction, or to treat secondary recurrent ulcerations. Percutaneous Achilles tendon lengthening and subtalar arthrodesis were added as needed. Wound healing problems, time to fusion and full weight-bearing in the prosthesis, complications in the prosthesis, and the ambulatory status were assessed. Satisfaction and function were evaluated by the AmpuPro score and the validated Prosthesis Evaluation Questionnaire scale. RESULTS Five patients had successful soft tissue healing and fusions but died of their underlying disease 2 to 46 months after the operation. Two diabetic patients required a transtibial amputation. The other 17 patients were followed for 27 months (range, 13-63). The average age of the 4 women and 13 men was 53.9 years (range, 16-87). Postoperative complications included minor wound healing problems in 8 patients, wound breakdown requiring revision in 4, phantom pain in 3, residual equinus in 1, and adjacent scar carcinoma in 1 patient. The time to full weight-bearing in the prosthesis ranged from 6 to 24 weeks (mean 10). The mean AmpuPro score was 107 points (of 120), and the mean Prosthesis Evaluation Questionnaire scale was 147 points (of 200). No complications occurred with the prosthesis. Twelve patients lost 1 to 2 mobility classes (mean 0.9). The arthrodeses all healed within 2.5 months (range, 1.5 to 5 months). CONCLUSION Adding an ankle arthrodesis to a Chopart's amputation either immediately or in a delayed fashion to treat anterior soft tissue complications was a successful salvage in most patients at this amputation level. It enabled the patients to preserve the advantages of a full-length limb with terminal weight-bearing. LEVEL OF EVIDENCE Level IV, retrospective case series.

Salvage Radiotherapy After Radical Prostatectomy

Salvage radiation therapy is the sole curative treatment for patients experiencing biochemical relapse after radical surgical treatment of prostate cancer. The main dilemma in salvage radiation therapy is, whether or not biochemical relapse represents purely localized recurrent disease in the prostatic fossa or systemic micrometastasis. Initiating salvage radiation therapy at an early time point raises its chances of success, but may lead to overtreatment of patients. Target volume definition and treatment techniques are a matter of current research, with still many questions unanswered. Strategies of treatment escalation either by increasing the treatment dose or combining radiation therapy with androgen deprivation therapy are being addressed in clinical trials.

Secondary succession and dipterocarp recruitment in Bornean rain forest after logging

To understand succession in dipterocarp rain forest after logging, the structure, species composition and dynamics of primary (PF) and secondary (SF) forest at Danum were compared. In 10 replicate 0.16-ha plots per forest type trees >= 10 cm gbh (3.2 cm dbh) were measured in 1995 and 2001. The SF had been logged in 1988, which allowed successional change to be recorded at 8 and 13 years. In 2001, saplings (1.0-3.1 cm dbh) were measured in nested quadrats. The forest types were similar in mean radiation at 2 m height, and in density, basal area and species number of all trees. Among small (10 <= 31.4) and large ( >= 31.4 cm gbh) trees, in both 1995 and 2001, there were 10- and 3-fold more dipterocarps in SF than PF respectively; and averaging over the two dates, there were correspondingly ca. 10- and 18-fold more pioneers. Mortality was ca. 60% higher in SF than PF, largely due to a seven-fold difference for pioneers: for dipterocarps there was little difference. Recruitment was similar in PF and SE Stem growth rates were 37% higher in SF than PF for all trees, although dipterocarps showed the opposite trend. Among saplings, dipterocarps dominated SF with a 10-fold higher density than in PF. For dipterocarps, the light (LH) and medium-heavy (MHH) canopy hardwoods, and the shade-tolerant, smaller-stature other (OTH) species (e.g. Hopea and Vatica) were in the ratios ca. 40:15:45 in SF and 85: < 1:15 in PF. LHs had higher mortality than OTHs in SE In PF ca. 80% of the saplings were LH: in SF ca. 70% were OTH. The predominance of OTHs in SF is explained by the logging of primary rain forest which was in a likely late stage of recovery from natural disturbance, plus the continuing shaded conditions in the understorey promoted by dense pioneer vegetation. At 13 years after logging succession appeared to be inhibited: LHs were being suppressed but MHHs and OTHs persisted. Succession in lowland dipterocarp, rain forests may therefore depend on the successional state of the primary forest when it is logged. A review of logged versus unlogged studies in Borneo highlights the need for more detailed ecological comparisons.

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10

PURPOSE Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.

MRI of hip osteoarthritis and implications for surgery

Osteoarthritis of the hip joint is caused by a combination of intrinsic factors and extrinsic factors. Different surgical techniques are being performed to delay or halt osteoarthritis. Success of salvage procedures of the hip depends on the existing cartilage and joint damage before surgery; the likelihood of therapy failure rises with advanced osteoarthritis. For imaging of intra-articular hip pathology, MR imaging represents the best technique because of its ability to directly visualize cartilage, superior soft tissue contrast, and the prospect of multidimensional imaging. This article gives an overview on the standard MR imaging techniques used for diagnosis of hip osteoarthritis and their implications for surgery.

Outcomes of patients on dual-boosted PI regimens: experience of the Swiss HIV cohort study

Dual-boosted protease inhibitors (DBPI) are an option for salvage therapy for HIV-1 resistant patients. Patients receiving a DBPI in the Swiss HIV Cohort Study between January1996 and March 2007 were studied. Outcomes of interest were viral suppression at 24 weeks. 295 patients (72.5%) were on DBPI for over 6 months. The median duration was 2.2 years. Of 287 patients who had HIV-RNA >400?copies/ml at the start of the regimen, 184 (64.1%) were ever suppressed while on DBPI and 156 (54.4%) were suppressed within 24 weeks. The median time to suppression was 101 days (95% confidence interval 90-125 days). The median number of past regimens was 6 (IQR, 3-8). The main reasons for discontinuing the regimen were patient's wish (48.3%), treatment failure (22.5%), and toxicity (15.8%). Acquisition of HIV through intravenous drug use and the use of lopinavir in combination with saquinavir or atazanavir were associated with an increased likelihood of suppression within 6 months. Patients on DBPI are heavily treatment experienced. Viral suppression within 6 months was achieved in more than half of the patients. There may be a place for DBPI regimens in settings where more expensive alternates are not available.

Proximal row carpectomy in emergency

Proximal row carpectomy (PRC) is a well-accepted procedure for the treatment of early post-traumatic degenerative disease of the wrist. Much less frequently, PRC has been advocated as an emergency procedure for irreparable fracture-dislocation of the wrist. Our objective was to compare the results of PRC in patients having undergone this procedure in the two contexts. We conducted a retrospective analysis of the clinical and radiographic results of six patients treated by emergency PRC as compared to six patients who underwent elective PRC. The mean follow-up was 36 months. Both the patient's satisfaction and the grasp of the wrist joint were significantly better in patients who underwent PRC emergency as compared to those having undergone elective PRC. Quick DASH score, radiographic results, and return to work were also more favourable in these patients, but the difference between the two groups was not significant. This study confirms that PRC is a valuable salvage technique indicated in early posttraumatic wrist collapse. Moreover, when performed in emergency, the procedure shows even better subjective and objective results, allowing a majority of patients to return to their previous job.

Endovascular Revascularization of Below-the-Knee Arteries: Prospective Short-Term Angiographic and Clinical Follow-up

PURPOSE: To evaluate arterial lesion characteristics and their impact on angiographic and clinical outcomes after endovascular below-the-knee (BTK) revascularization. MATERIALS AND METHODS: Between April 2008 and June 2009, 33 patients (mean age 74.9 years) with 34 limbs and 50 arterial segments (mean lesion length 59.3 mm) undergoing endovascular BTK revascularization agreed to undergo prospective clinical and intraarterial angiographic 6-month follow-up evaluation. Clinical indication for BTK revascularization was critical limb ischemia (CLI) in 18 patients and delayed wound healing without hemodynamic evidence of CLI and intermittent claudication (IC) in 15 patients. RESULTS: Binary restenosis was observed in 40% of treated segments at 6 months. Primary sustained clinical improvement was 82.4% and 55.9% at 3 months and 6 months. Lesion length was independently associated with binary restenosis (hazard ratio [HR] 1.013, 95% confidence interval [CI] 1.000-1.016, P = .05) and lower rates of primary sustained clinical improvement (HR 1.024, 95% CI 1.006-1.042, P = .008). CONCLUSIONS: Endovascular BTK revascularization yields clinical and angiographic benefits both for patients with IC and for patients with CLI. Although arterial lesion length adversely affects angiographic and clinical outcomes after endovascular revascularization, limb salvage rates were substantially higher compared with the comparatively low patency rates after BTK angioplasty.

Basilar artery occlusion

The clinical presentation of basilar artery occlusion (BAO) ranges from mild transient symptoms to devastating strokes with high fatality and morbidity. Often, non-specific prodromal symptoms such as vertigo or headaches are indicative of BAO, and are followed by the hallmarks of BAO, including decreased consciousness, quadriparesis, pupillary and oculomotor abnormalities, dysarthria, and dysphagia. When clinical findings suggest an acute brainstem disorder, BAO has to be confirmed or ruled out as a matter of urgency. If BAO is recognised early and confirmed with multimodal CT or MRI, intravenous thrombolysis or endovascular treatment can be undertaken. The goal of thrombolysis is to restore blood flow in the occluded artery and salvage brain tissue; however, the best treatment approach to improve clinical outcome still needs to be ascertained.

An Evaluation of Compression Schemes for Wireless Networks

Data gathering, either for event recognition or for monitoring applications is the primary intention for sensor network deployments. In many cases, data is acquired periodically and autonomously, and simply logged onto secondary storage (e.g. flash memory) either for delayed offline analysis or for on demand burst transfer. Moreover, operational data such as connectivity information, node and network state is typically kept as well. Naturally, measurement and/or connectivity logging comes at a cost. Space for doing so is limited. Finding a good representative model for the data and providing clever coding of information, thus data compression, may be a means to use the available space to its best. In this paper, we explore the design space for data compression for wireless sensor and mesh networks by profiling common, publicly available algorithms. Several goals such as a low overhead in terms of utilized memory and compression time as well as a decent compression ratio have to be well balanced in order to find a simple, yet effective compression scheme.

Adjuvant or radical fractionated stereotactic radiotherapy for patients with pituitary functional and nonfunctional macroadenoma

Purpose To evaluate the efficacy and toxicity of stereotactic fractionated radiotherapy (SFRT) for patients with pituitary macroadenoma (PMA). Methods and Materials Between March 2000 and March 2009, 27 patients (male to female ratio, 1.25) with PMA underwent SFRT (median dose, 50.4 Gy). Mean age of the patients was 56.5 years (range, 20.3 - 77.4). In all but one patient, SFRT was administered for salvage treatment after surgical resection (transphenoidal resection in 23, transphenoidal resection followed by craniotomy in 2 and multiple transphenoidal resections in another patient). In 10 (37%) patients, the PMAs were functional (3 ACTH-secreting, 3 prolactinomas, 2 growth hormone-secreting and 2 multiple hormone-secretion). Three (11.1%) and 9 (33.3%) patients had PMA abutting and compressing the optic chiasm, respectively. Mean tumor volume was 2.9 ± 4.6 cm3. Eighteen (66.7%) patients had hypopituitarism prior to SFRT. The mean follow-up period after SFRT was 72.4 ± 37.2 months. Results Tumor size decreased for 6 (22.2%) patients and remained unchanged for 19 (70.4%) other patients. Two (7.4%) patients had tumor growth inside the prescribed treatment volume. The estimated 5-year tumor growth control was 95.5% after SFRT. Biochemical remission occurred in 3 (30%) patients with functional PMA. Two patients with normal anterior pituitary function before SFRT developed new deficits 25 and 65 months after treatment. The 5-year survival without new anterior pituitary deficit was thus 95.8%. Five patients with visual field defect had improved visual function and 1 patient with no visual defect prior to SFRT, but an optic chiasm abutting tumor, had a decline in visual function. The estimated 5-year vision and pituitary function preservation rates were 93.2% and 95.8%, respectively. Conclusions SFRT is a safe and effective treatment for patients with PMA, although longer follow-up is needed to evaluate long-term outcomes. In this study, approximately 1 patient with visual field defect out of two had an improved visual function.

Chapter IV: Treatment of critical limb ischaemia

Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural.

Autologous peripheral blood stem cell transplantation for acute myeloid leukemia

We report the results of a prospective, randomized phase 3 trial evaluating autologous peripheral blood stem cell transplantation (ASCT) versus intensive consolidation chemotherapy in newly diagnosed AML patients in complete remission (CR1). Patients with AML (16-60 years) in CR1 after 2 cycles of intensive chemotherapy and not eligible for allogeneic SCT were randomized between intensive chemotherapy with etoposide and mitoxantrone or ASCT ater high-dose cyclophosphamide and busulfan. Of patients randomized (chemotherapy, n = 259; ASCT, n = 258), more than 90% received their assigned treatment. The 2 groups were comparable with regard to prognostic factors. The ASCT group showed a markedly reduced relapse rate (58% vs 70%, P = .02) and better relapse-free survival at 5 years (38% vs 29%, P = .065, hazard ratio = 0.82; 95% confidence interval, 0.66-1.1) with nonrelapse mortality of 4% versus 1% in the chemotherapy arm (P = .02). Overall survival was similar (44% vs 41% at 5 years, P = .86) because of more opportunities for salvage with second-line chemotherapy and stem cell transplantation in patients relapsing on the chemotherapy arm. This large study shows a relapse advantage for ASCT as postremission therapy but similar survival because more relapsing patients on the chemotherapy arm were salvaged with a late transplantation for relapse. This trial is registered at www.trialregister.nl as #NTR230 and #NTR291.