Paediatric Anatomical Models in Radiotherapy Applications.

Anatomical models have key applications in radiotherapy, notably to help understand the relationship between radiation dose and risk of developing side effects. This review analyses whether age-specific computational phantoms, developed from healthy subjects and paediatric cancer patient data, are adequate to model a paediatric population. The phantoms used in the study were International Commission on Radiological Protection (ICRP), 4D extended cardiac torso (XCAT) and Radiotherapy Paediatric Atlas (RT-PAL), which were also compared to literature data. Organ volume data for 19 organs was collected for all phantoms and literature. ICRP was treated as the reference for comparison, and percentage difference (P.D) for the other phantoms were calculated relative to ICRP. Overall comparisons were made for each age category (1, 5, 10, 15) and each organ. Statistical analysis was performed using Microsoft Excel (version 16.59). The smallest P.D to ICRP was for Literature (-17.4%), closely followed by XCAT (26.6%). The largest was for RT-PAL (88.1%). The rectum had the largest average P.D (1,049.2%) and the large bowel had the smallest (2.0%). The P.D was 122.6% at age 1 but this decreased to 43.5% by age 15. Linear regression analysis showed a correlation between organ volume and age to be the strongest for ICRP (R2 = 0.943) and weakest for XCAT (R2 = 0.676). The phantoms are similar enough to ICRP for potential use in modelling paediatric populations. ICRP and XCAT could be used to model a healthy population, whereas RT-PAL could be used for a population undergoing/after radiotherapy.

Comparative genomic characterization of melanoma of known and unknown primary

BackgroundThis study aims to genomically characterize melanoma of unknown primary (MUP) in comparison to melanomas of cutaneous primary (MCP).MethodsEligible cases were collected from the MSK-IMPACT™ Clinical Sequencing Cohort published in the cBioPortal database. Genomic analysis was performed using a hybridization-capture-based next-generation sequencing assay designed to detect mutations, small insertions and deletions, copy number alterations, and genomic rearrangements.ResultsAmong 462 patients of whom 18.4% had MUP, brain metastasis was more common among patients with MUP (23% vs 7.1%). The differences in genomic profiling between MCP and MUP did not reach statistical significance. The 187 MCP and 44 MUP patients treated with immune checkpoint inhibitors had a median overall survival of 49 and 44 months, respectively (p = 0.705).ConclusionsThe differences in somatic mutation patterns and survival outcomes were not statistically significant. These findings may allude to similar carcinogenic processes but should be considered exploratory and interpreted with caution. (AU)

Comparative genomic characterization of melanoma of known and unknown primary.

BACKGROUND: This study aims to genomically characterize melanoma of unknown primary (MUP) in comparison to melanomas of cutaneous primary (MCP). METHODS: Eligible cases were collected from the MSK-IMPACT™ Clinical Sequencing Cohort published in the cBioPortal database. Genomic analysis was performed using a hybridization-capture-based next-generation sequencing assay designed to detect mutations, small insertions and deletions, copy number alterations, and genomic rearrangements. RESULTS: Among 462 patients of whom 18.4% had MUP, brain metastasis was more common among patients with MUP (23% vs 7.1%). The differences in genomic profiling between MCP and MUP did not reach statistical significance. The 187 MCP and 44 MUP patients treated with immune checkpoint inhibitors had a median overall survival of 49 and 44 months, respectively (p = 0.705). CONCLUSIONS: The differences in somatic mutation patterns and survival outcomes were not statistically significant. These findings may allude to similar carcinogenic processes but should be considered exploratory and interpreted with caution.

The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer.

AIMS: Despite recent advances in the primary and secondary prevention of cervical cancer, a significant number of women present with or develop metastatic disease. There is currently no consensus on the standard of care for second-line systemic treatment of recurrent/metastatic cervical cancer. The purpose of this study was to evaluate the second-line systemic therapy used and the associated outcomes in a single cancer centre. MATERIALS AND METHODS: A retrospective review of patients with cervical cancer who received one or more lines of treatment for recurrent or metastatic cervical cancer at the Royal Marsden Hospital between 2004 and 2014 was carried out. The primary objective was to establish the types of second-line systemic treatment used. Secondary end points included objective response rate, progression-free survival and overall survival after second-line therapy. RESULTS: In total, 75 patients were included in the study; 53 patients (70.7%) received second-line therapy for recurrent/metastatic disease. The most common second-line therapy was weekly paclitaxel (28.3%). Carboplatin-based chemotherapy (24.5%), targeted agent monotherapy within clinical trials (22.6%), docetaxel-based chemotherapy (13.2%), topotecan (9.4%) and gemcitabine (1.9%) were also used. The objective response rate to second-line therapy was 13.2%, which included three partial responses to carboplatin and paclitaxel, two partial responses to docetaxel-based chemotherapy, one partial response to weekly paclitaxel and one partial response to cediranib. Twenty-two patients (41.5%) achieved stable disease at 4 months. The median progression-free survival for women treated with second-line therapy was 3.2 months (95% confidence interval 2.1-4.3) and median overall survival was 9.3 months (95% confidence interval 6.4-12.5). Thirty-nine per cent of patients received third-line therapy. CONCLUSION: Seventy per cent of patients treated with first-line systemic therapy for recurrent/metastatic cervical cancer subsequently received second-line treatment but response rates were poor. There remains no standard of care for second-line systemic therapy for advanced cervical cancer. Patients should be considered for clinical trials whenever feasible, including novel targeted agents and immunotherapy.

Renal cell carcinoma in pregnancy: a rare coexistence

Renal cell carcinoma (RCC) is rarely diagnosed during pregnancy and its management represents a real challenge. As the symptomatology might mimic other common pregnancy-related disorders, the diagnosis is often delayed. RCC should be considered in women of childbearing age who present with recurrent or refractory urinary tract symptoms, flank pain, or a palpable mass. Ultrasound appears to be the imaging procedure of choice followed by the magnetic resonance imaging for evaluating the urinary system in pregnant women. The probability of cure is directly related to the stage or degree of tumor dissemination. Surgical resection is the mainstay of treatment (AU)

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Renal cell carcinoma in pregnancy: a rare coexistence.

Renal cell carcinoma (RCC) is rarely diagnosed during pregnancy and its management represents a real challenge. As the symptomatology might mimic other common pregnancy-related disorders, the diagnosis is often delayed. RCC should be considered in women of childbearing age who present with recurrent or refractory urinary tract symptoms, flank pain, or a palpable mass. Ultrasound appears to be the imaging procedure of choice followed by the magnetic resonance imaging for evaluating the urinary system in pregnant women. The probability of cure is directly related to the stage or degree of tumor dissemination. Surgical resection is the mainstay of treatment.

Lung cancer in pregnancy: report of nine cases from an international collaborative study.

OBJECTIVE: Lung cancer is an uncommon diagnosis during pregnancy. The combination of smoking in young women, increased maternal age during pregnancy, and increasing incidence of lung cancer worldwide may cause an increase of pregnancy associated lung cancer. The aim of this study was to describe all cases of lung cancer during pregnancy, registered in the international Cancer in Pregnancy registration study (CIP study; www.cancerinpregnancy.org). MATERIALS AND METHODS: We present nine cases, all advanced lung cancer during the course of pregnancy. Collected data included demographic features of the study patients, cancer treatment, pregnancy outcome as well as maternal and fetal outcomes. RESULTS AND CONCLUSION: Nine pregnant patients from 4 European centres with a median age of 33 years old (range, 26-42) were included. The median gestational age at diagnosis was 17 weeks (range, 6-28). All patients presented with metastatic disease including bone, lung, brain, spinal cord, pleura, lymph nodes, adrenal and liver. Histopathology was compatible with adenocarcinoma in 4 patients, non-small cell lung cancer with unidentified subtype in 2 patients and squamous-cell, large-cell and a poorly differentiated carcinoma in 3 patients, respectively. Eight patients were treated with systemic therapy, five of them during gestation. No responses were seen. The maternal postpartum outcome was poor with less than one year survival following delivery. One patient experienced a spontaneous abortion and three pregnancies were terminated. Five infants were all born premature due to poor maternal status by cesarean section, with a median gestational age of 30 weeks (range 26-33). To summarize, lung cancer in pregnancy has a dismal maternal outcome in our series. We add nine new cases and discuss both therapeutic and prognostic results.