EXclusion of non-Involved uterus from the Target Volume (EXIT-trial): An individualized treatment for locally advanced cervical cancer using modern radiotherapy and imaging techniques

Background: Definitive chemoradiotherapy is standard of care in locally advanced cervical cancer (LACC). Both toxicity and local relapse remain major concerns in this treatment. We hypothesize that a magnetic resonance imaging (MRI) based redefining of the radiotherapeutic target volume will lead to a reduction of acute and late toxicity. In our center, chemoradiotherapy followed by hysterectomy was implemented successfully in the past. This enables us to assess the safety of reducing the target volume but also to explore the biological effects of chemoradiation on the resected hysterectomy specimen. Methods: The EXIT-trial is a phase II, single arm study aimed at LACC patients. This study evaluates whether a MRI-based exclusion of the non-tumor-bearing parts of the uterus out of the target volume results in absence of tumor in the non-high doses irradiated part of the uterus in the hysterectomy specimen. Secondary endpoints include a dosimetric comparison of dose on normal tissue when comparing study treatment plans compared to treatment of the whole uterus at high doses; acute and chronic toxicity, overall survival, local relapse- and progression-free survival. In the translational part of the study, we will evaluate the hypothesis that the baseline apparent diffusion coefficient (ADC) values of diffusion weighted MRI and its evolution 2 weeks after start of CRT, for the whole tumor as well as for intra-tumoral regions, is prognostic for residual tumor on the hysterectomy specimen. Discussion: Although MRI is already used to guide target delineation in brachytherapy, the EXIT-trial is the first to use this information to guide target delineation in external beam radiotherapy. Early therapy resistance prediction using DW-MRI opens a window for early treatment adaptation or further dose-escalation on tumors/intratumoral regions at risk for treatment failure

Hydrological Response of Catchment Management in the North Ethiopian Highlands

status: publishe

Impact of soil and water conservation measures on catchment hydrological response—a case in north Ethiopia

Impact studies of catchment management in the developing world rarely include detailed hydrological components. Here, changes in the hydrological response of a 200-ha catchment in north Ethiopia are investigated. The management included various soil and water conservation measures such as the construction of dry masonry stone bunds and check dams, the abandonment of post-harvest grazing, and the establishment of woody vegetation. Measurements at the catchment outlet indicated a runoff depth of 5 mm or a runoff coefficient (RC) of 1•6% in the rainy season of 2006. Combined with runoff measurements at plot scale, this allowed calculating the runoff curve number (CN) for various land uses and land management techniques. The pre-implementation runoff depth was then predicted using the CN values and a ponding adjustment factor, representing the abstraction of runoff induced by the 242 check dams in gullies. Using the 2006 rainfall depths, the runoff depth for the 2000 land management situation was predicted to be 26•5 mm (RC = 8%), in line with current RCs of nearby catchments. Monitoring of the ground water level indicated a rise after catchment management. The yearly rise in water table after the onset of the rains ( T) relative to the water surplus (WS) over the same period increased between 2002-2003 ( T/WS = 3•4) and 2006 ( T/WS >11•1). Emerging wells and irrigation are other indicators for improved water supply in the managed catchment. Cropped fields in the gullies indicate that farmers are less frightened for the destructive effects of flash floods. Due to increased soil water content, the crop growing period is prolonged. It can be concluded that this catchment management has resulted in a higher infiltration rate and a reduction of direct runoff volume by 81% which has had a positive influence on the catchment water balance.status: publishe

Impact of soil and water conservation measures on catchment hydrological response: a case in north Ethiopia

Impact studies of catchment management in the developing world rarely include detailed hydrological components. Here, changes in the hydrological response of a 200-ha catchment in north Ethiopia are investigated. The management included various soil and water conservation measures such as the construction of dry masonry stone bunds and check dams, the abandonment of post-harvest grazing, and the establishment of woody vegetation. Measurements at the catchment outlet indicated a runoff depth of 5 mm or a runoff coefficient (RC) of 1?6% in the rainy season of 2006. Combined with runoff measurements at plot scale, this allowed calculating the runoff curve number (CN) for various land uses and land management techniques. The pre-implementation runoff depth was then predicted using the CN values and a ponding adjustment factor, representing the abstraction of runoff induced by the 242 check dams in gullies. Using the 2006 rainfall depths, the runoff depth for the 2000 land management situation was predicted to be 26?5 mm (RC D 8%), in line with current RCs of nearby catchments. Monitoring of the ground water level indicated a rise after catchment management. The yearly rise in water table after the onset of the rains ( T) relative to the water surplus (WS) over the same period increased between 2002-2003 ( T/WS D 3?4) and 2006 ( T/WS >11?1). Emerging wells and irrigation are other indicators for improved water supply in the managed catchment. Cropped fields in the gullies indicate that farmers are less frightened for the destructive effects of flash floods. Due to increased soil water content, the crop growing period is prolonged. It can be concluded that this catchment management has resulted in a higher infiltration rate and a reduction of direct runoff volume by 81% which has had a positive influence on the catchment water balance

Pembrolizumab, radiotherapy, and an immunomodulatory five-drug cocktail in pretreated patients with persistent, recurrent, or metastatic cervical or endometrial carcinoma: Results of the phase II PRIMMO study

A phase II study (PRIMMO) of patients with pretreated persistent/recurrent/metastatic cervical or endometrial cancer is presented. Patients received an immunomodulatory five-drug cocktail (IDC) consisting of low-dose cyclophosphamide, aspirin, lansoprazole, vitamin D, and curcumin starting 2 weeks before radioimmunotherapy. Pembrolizumab was administered three-weekly from day 15 onwards; one of the tumor lesions was irradiated (8Gyx3) on days 15, 17, and 19. The primary endpoint was the objective response rate per immune-related response criteria (irORR) at week 26 (a lower bound of the 90% confidence interval [CI] of > 10% was considered efficacious). The prespecified 43 patients (cervical, n = 18; endometrial, n = 25) were enrolled. The irORR was 11.1% (90% CI 2.0–31.0) in cervical cancer and 12.0% (90% CI 3.4–28.2) in endometrial cancer. Median duration of response was not reached in both cohorts. Median interval-censored progression-free survival was 4.1 weeks (95% CI 4.1–25.7) in cervical cancer and 3.6 weeks (95% CI 3.6–15.4) in endometrial cancer; median overall survival was 39.6 weeks (95% CI 15.0–67.0) and 37.4 weeks (95% CI 19.0–50.3), respectively. Grade ≥ 3 treatment-related adverse events were reported in 10 (55.6%) cervical cancer patients and 9 (36.0%) endometrial cancer patients. Health-related quality of life was generally stable over time. Responders had a significantly higher proportion of peripheral T cells when compared to nonresponders (p = 0.013). In conclusion, PRIMMO did not meet its primary objective in both cohorts; pembrolizumab, radiotherapy, and an IDC had modest but durable antitumor activity with acceptable but not negligible toxicity. Trial registration ClinicalTrials.gov (identifier NCT03192059) and EudraCT Registry (number 2016-001569-97)

Algorithms for molecular testing in solid tumours

n order to advise the Federal Government on the reimbursement of molecular tests related to Personalised Medicine in Oncology, the Commission of Personalised Medicine (ComPerMed), represented by Belgian experts, has developed a methodology to classify molecular testing in oncology. The different molecular tests per cancer type are represented in algorithms and are annotated with a test level reflecting their relevance based on current guidelines, drug approvals and clinical data. The molecular tests are documented with recent literature, guidelines and a brief technical description. This methodology was applied on different solid tumours for which molecular testing is a clear clinical need