Clear Cell Renal Cell Carcinoma: Deep Learning-Based Prediction of Tumor Grade from Contrast-Enhanced CT

Tumor grading is an important prognostic parameter for renal cell carcinoma (RCC). However, current grading schemes require an invasive surgical procedure, putting patients at risks including increased risk of hemorrhage, infection, renal failure, or death. Furthermore, low grade RCC is indolent with low mortality risk and may not require treatment. Therefore, a pre-operative and non-invasive assessment of malignancy grade may be beneficial and facilitate optimal timing of treatment. In recent years, deep learning-based image analysis has gained wide popularity in cancer prognosis and prediction. The goal of this study is to investigate the feasibility and performance of a deep-learning-based model for clear cell RCC grading prediction from contrast-enhance computed tomography (CECT). After institutional review board approval, an institutional pathology database was queried for all renal biopsies between December 2002 and October 2018. All included patients received a CT with a non-contrast and at least one post-contrast series. All patients have Fuhrman grade confirmation from surgical pathology, with CT scan prior to the procedure. Tumors were manually annotated by a radiologist on either the corticomedullary or nephrographic phase CECT. Rectangular regions of interest (ROI) were drawn on each slice throughout the tumor and used as inputs to the Deep CNN ResNet50. A binary label of low grade or high grade was assigned to each patient. Sensitivity, specificity, accuracy, and AUC were calculated based on a five-fold cross-validation. Preliminary results from a small subset of data suggests that a deep learning model can be used to predict clear cell RCC grading based on CT imaging prior to surgical procedures

Magnetic ressonance imaging in staging and prognostic evaluation of patients with cervical carcinoma treated with concurrent chemotheradiotherapy

Orientador: Luiz Carlos ZeferinoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: Introdução: A despeito do tratamento para o carcinoma de colo uterino, 30% das mulheres não obtêm resposta total e morrem precocemente, devido à recorrência ou persistência da doença. O método de imagem e o momento ideal para avaliar a resposta terapêutica, bem como fatores prognosticos destas pacientes, permanecem indefinidos. Objetivo: Avaliar as contribuições da Ressonância Magnética no estadiamento e na identificação de fatores prognósticos relevantes em pacientes submetidas a tratamento concomitante de quimioterapia e radioterapia, seguido de braquiterapia Sujeito e métodos: estudo de coorte longitudinal, com seguimento antes e após o tratamento das mulheres. Foram selecionadas 56 pacientes, com diagnóstico de carcinoma de colo uterino, tratadas com quimioterapia e radioterapia concomitantes seguido de braquiterapia e acompanhadas no HCII - INCA.Todas foram submetidas a Ressonâncias magnéticas seriadas, sendo a primeira no momento do estadiamento, a segunda após o tratamento concomitante e a terceira após a braquiterapia. Os fatores prognósticos estudados foram: volume tumoral e invasão de corpo uterino, medidos na primeira RM. As respostas ao tratamento foram subdividas de acordo com os criterios de RECIST em resposta completa, resposta parcial, doença estável e progressão de doença, e foram mensuradas no momento da segunda RM após o tratamento combinado e no momneto da terceira RM após a braquiterapia. Análise estatística: a concordância foi avaliada através do coeficiente de Kappa. A sobrevida foi avaliada pelo método de Kapplan-Meier e as curvas foram comparadas pelo teste de log-rank. Foram utilizados modelos de COX (simples e múltiplos) para calcular o Hazard Ratio. O nível de significância foi de 5% e o software utilizado foi o SAS versão 9.1.3. Resultados: O índice de Kappa entre estadiamento FIGO e o estadiamento com RM foi de 0,40. Na segunda RM após o tratamento concomitante, 1 paciente apresentou doença estável, 1 progressão de doença, 20 resposta parcial e 21 obtiveram resposta completa. Na terceira RM, após a braquiterapia, 4 tiveram progressão da doença, 4 resposta parcial e 33 obtiveram resposta completa. Pacientes com volume tumoral maior que 50cm3 tiveram sobrevida global pior. Conclusão: A concordância entre o estadiamento FIGO e o estadiamento com RM foi baixa. O volume tumoral mostrou ser um bom preditor de sobrevida global mesmo quando corrigido em análises multivaridas para o estadiamento FIGO. A invasão do corpo uterino mostrou-se limítrofe como fator de sobrevida globalAbstract: Introduction: Despite the available treatment for cervical cancer, 30% of women fail to achieve full response to therapy and die early due to recurrence or persistence of the disease. The ideal imaging method and the optimal time for evaluating therapeutic response, as well as the prognostic factors in these patients, remain undefined. Objective: To evaluate the contributions of magnetic resonance imaging (MRI) in staging and in the identification of relevant prognostic factors in patients submitted to treatment consisting of concurrent chemoradiotherapy followed by brachytherapy. The agreement between FIGO and MRI staging was also evaluated. Subjects and Methods: A longitudinal, cross sectional study with evaluations prior to and following treatment was carried out in 56 women with a diagnosis of cervical cancer treated with concurrent chemoradiotherapy followed by brachytherapy at the II Cancer Hospital of the National Cancer Institute (INCA). All patients were submitted to serial MRI, the first being carried out at the time of staging, the second following concurrent chemoradiotherapy and the third after brachytherapy. The prognostic factors studied were tumor volume and uterine invasion at first MRI. The responses to treatment were subdivided according to the Response Evaluation Criteria in Solid Tumors (RECIST) into complete response, partial response, stable disease or disease progression, and were assessed at the time of the second MRI following combined treatment and at the time of the third MRI after brachytherapy. Statistical Analysis: Agreement was evaluated using the kappa coefficient. Survival was assessed using the Kaplan-Meier method and the curves were compared using the log-rank test. Univariate and multivariate Cox models were used to calculate the hazard ratios. Statistical significance was defined at 5% and the statistical software package used was SAS, version 9.1.3. Results: The kappa index between FIGO staging and MRI-based staging was 0.40. At the second MRI after concurrent chemoradiotherapy, 1 patient was found to have stable disease, 1 had disease progression, 20 had achieved a partial response and 21 had achieved complete response. At the third MRI, following brachytherapy, 4 patients had disease progression, 4 had a partial response and 33 had obtained complete response. Overall survival was poorer in patients in whom tumor volume was > 50 cm3. Conclusion: Agreement between FIGO staging and MRI staging was low. Tumor volume was found to be a good predictor of overall survival even when corrected for FIGO staging in multivariate analyses. Uterine invasion was found to be a borderline predictive factor of overall survivalMestradoCiencias BiomedicasMestre em Tocoginecologi

Time to Diagnosis of Second Primary Cancers among Patients with Breast Cancer

Many breast cancer diagnoses and second cancers are associated with BRCA gene mutations. Early detection of cancer is necessary to improve health outcomes, particularly with second cancers. Little is known about the influence of risk factors on time to diagnosis of second primary cancers after diagnosis with BRCA-related breast cancer. The purpose of this cohort study was to examine the risk of diagnosis of second primary cancers among women diagnosed with breast cancer after adjusting for BRCA status, age, and ethnicity. The study was guided by the empirical evidence supporting the mechanism of action in the mutation of BRCA leading to the development of cancer. Composite endpoint was used to define second primary cancer occurrences, and Kaplan-Meier survival curves were used to compare the median time-to-event among comparison groups and BRCA gene mutation status. Cox proportional hazards was used to examine the relationships between age at diagnosis, ethnicity, BRCA gene mutation status, and diagnosis of a second primary cancer. The overall median time to event for diagnosis of second primary cancers was 14 years. The hazard ratios for BRCA2 = 1.47, 95% CI [1.03 - 2.11], White = 1.511, 95% CI [1.18 - 1.94], and American Indian/Hawaiian = 1.424, 95% CI [1.12 -1.81] showing positive significant associations between BRCA2 mutation status and risk of diagnosis of second primary colorectal, endometrial, cervical, kidney, thyroid, and bladder cancers. Data on risk factors for development of second cancers would allow for identification of appropriate and timely screening procedures, determining the best course of action for prevention and treatment, and improving quality of life among breast cancer survivors

Estramustine and its Derivatives in Potentiating Radiotherapy of Prostate Cancer

The purpose of this study was to deepen our knowledge of the combined use of estramustine and radiotherapy in the treatment of prostate cancer. Prostate cancer is a common disease, with a high variability between subjects in its malignant potential. In many cases, the disease is an incidental finding with little or no clinical significance. In other cases, however, prostate cancer may be an aggressive malignant disease, which, if the initial treatment fails, lacks an effective cure and may lead to severe symptoms, metastasis, and death despite all treatment. In many cases, the methods of treatment available at the moment provide cure or significant regression of symptoms, but often at the cost of considerable side effects. Estramustine, a cytostatic drug used for treating advanced cancer of the prostate, has been shown to inhibit prostate cancer progression and also to increase the sensitivity of cancer cells to radiotherapy. The goals of this study were, first, to find out whether it is possible to use either estramustine or an antibody against estramustine binding protein as carrier molecules for bringing therapeutic radioisotopes into prostate cancer cells, and, secondly, to gain more understanding of the mechanisms behind the known radiosensitising effect of estramustine. Estramustine and estramustine binding protein antibody were labelled with iodine-125 to study the biodistribution of these substances in mice. In the first experiment, both of the substances accumulated in the prostate, but radioiodinated estramustine also showed affinity to the liver and the lungs. Since the radiolabelled antibody was found out to accumulate more selectively to the prostate, we studied its biodistribution in nude mice with DU-145 human prostate cancer implants. In this experiment, the prostate and the tumour accumulated more radioactivity than other organs, but we concluded that the difference in the dose of radiation compared to other organs was not sufficient for the radioiodinated antibody to be advocated as a carrier molecule for treating prostate cancer. Mice with similar DU-145 prostate cancer implants were then treated with estramustine and external beam irradiation, with and without neoadjuvant estramustine treatment. The tumours responded to the treatment as expected, showing the radiation potentiating effect of estramustine. In the third experiment, this effect was found without an increase in the amount of apoptosis in the tumour cells, despite previous suggestions to the contrary. In the fourth experiment, we gave a similar treatment to the mice with DU-145 tumours. A reduction in proliferation was found in the groups treated with radiotherapy, and an increased amount of tumour hypoxia and tumour necrosis in the group treated with both neoadjuvant estramustine and radiation. This finding is contradictory to the suggestion that the radiation sensitising effect of estramustine could be attributed to its angiogenic activity.Tässä työssä tutkittiin estramustiinin ja sädehoidon yhteisvaikutusta eturauhassyövän hoidossa. Eturauhassyöpä on yleinen sairaus, joka usein ilmenee sattumalöydöksenä eikä aiheuta oireita tai lyhennä elinaikaa. Tauti on kuitenkin luonteeltaan hyvin vaihteleva, ja joillakin potilailla se on agressiivinen sairaus, joka etenee kaikesta hoidosta huolimatta ja johtaa vaikeisiin oireisiin ja kuolemaan. Nykyaikainen hoito auttaa osassa tapauksista, mutta voi aiheuttaa vaikeita sivuvaikutuksia. Estramustiini on sytostaatti, jota on aiemmin käytetty hormonihoidolle reagoimattoman eturauhassyövän hoidossa. Sen on myös todettu herkistävän syöpäsoluja sädehoidon vaikutukselle. Estramustiini kertyy mm. eturauhassyöpäsolujen sisään sitojaproteiinin ansiosta. Tämän tutkimuksen tavoitteena oli selvittää, voidaanko estramustiinia tai sen sitojaproteiinin vasta-ainetta käyttää kantajamolekyyleinä viemään hoidossa käytettävää radioaktiivsta ainetta eturauhassyöpäsolujen sisään. Toisena tavoitteena oli saada lisätietoa sädeherkistävän vaikutuksen mekanismeista. Estramustiini- ja estramustiinin sitojaproteiinimolekyyleihin liitettiin radioaktiivista jodia ja tutkitiin aineiden kertymistä eri elimiin hiirillä. Molemmat aineet kertyivät eturauhaseen, radiojoditettu estramustiini myös maksaan ja keuhkoon. Radiojoditettu estramustiinin sitoja-aine kertyi selektiivisemmin eturauhaseen joten se valittiin jatkotutkimukseen. Kertymistä tutkittiin hiirillä, joilla oli DU-145-eturauhassyöpäsiirteet. Vasta-aineen kertyminen eturauhassyöpäsiirteeseen ei ollut muihin elimiin verrattuna niin voimakasta, että sitä voitaisiin suositella kantaja-aineeksi eturauhassyövän hoidossa. Samanlaisia hiirten DU-145-eturauhassyöpäsiirteitä hoidettiin sitten ulkoisella sädehoidolla, estramustiinilla ja näiden yhdistelmällä. Kasvaimien todettiin reagoivan hoidolle ja estramustiini tehosti sädehoidon vaikutusta. Toisin kuin odotettiin, tehon lisääntyminen ei liittynyt apoptoosin eli ohjelmoidun solukuoleman lisääntymiseen. Lisätutkimuksissa selvisi, että sädehoito vähensi kasvaimien solunjakautumista ja sädehoidon ja estramustiinin yhdistelmä aiheutti kasvaimiin hapenpuutetta ja lisäsi kuolioon menneiden solujen määrää. Tämä ei mielestämme tue aiempaa oletusta, jonka mukaan estramustiinin verenkiertoa parantava vaikutus kasvaimessa olisi osallisena sädeherkistyksessä

Improving Screening Strategies for Prostate Cancer

Th is thesis describes research on screening for prostate cancer. To improve understanding of the thesis, some background information will be provided in this introduction. First, a short description of the prostate and of prostate cancer will be given in Chapter 1, followed by more detailed background information on screening for prostate cancer in Chapter 2. Th e fi nal part of this introduction, Chapter 3, will outline the scope of this thesis

Gastric Carcinoma

Gastric cancer is one of the most common tumors worldwide. It has a heterogeneous milieu, where the genetic background, tumor immunology, oxidative stress, and microbial infections are key players in the multiple stages of tumorigenesis. These diverse factors are linked to the prognosis of the gastric cancer and the survival of gastric cancer patients. This book is appropriate for scientists and students in the field of oncology, gastroenterology, molecular biology, immunology, cell biology, biology, biochemistry, and pathology. This authoritative text carefully explains the fundamentals, providing a general overview of the principles followed by more detailed explanations of these recent topics efficiently. The topics presented herein contain the most recent knowledge in gastric cancer concerning the oncogenic signaling, genetic instability, the epigenetic aspect, molecular features and their clinical implications, miRNAs, integrin and E-cadherin, carbohydrate-associated-transferases, free radicals, immune cell responses, mucins, Helicobacter-pylori, neoadjuvant and adjuvant therapy, prophylactic strategy for peritoneal recurrence, and hepatic metastasis

An investigation of the detection and treatment of colorectal liver metastases

In the United Kingdom, colorectal cancer creates a significant health burden, with over 34 000 new cases diagnosed each year and over 16 000 deaths per year. Almost 50% of patients with colorectal cancer will develop liver metastases: up to 25% will have liver metastases at time of initial presentation with the remaining 25% developing liver metastases during the course of their disease. Death from hepatic metastases accounts for a large percentage of colorectal cancer mortalities and if left untreated the prognosis is poor, with median survival from 5 to 21 months with almost none alive at 5 years. Surgical resection offers the only potential curative treatment for colorectal liver metastases with the five year survival rate varying in the literature from 25% to 51%. Hepatic surgery was associated with high morbidity and mortality and it is only since the 1990s that an evidence base has been published showing improved long term outcomes. Radiological imaging plays an essential role in the detection and characterisation of colorectal liver metastases. Accurate staging of the disease allows patient selection for hepatic surgery. Despite recent and significant technological advances in radiological imaging, up to 50% of patients that have undergone curative partial hepatectomy will develop hepatic recurrence in the first two years after surgery. Evidence from growth rate studies has shown that colorectal liver metastases are slow growing and that these recurrences were present at the time of initial staging. Therefore, the problem of occult liver metastases remains. This thesis has assessed the potential clinical role of a new imaging modality in the detection of colorectal liver metastases: contrast enhanced ultrasound (CE-US). Initially a prospective trial using percutaneous CE-US with intravenous administration of an ultrasound contrast agent that has been used primarily in cardiac imaging was performed. The results of this study found that CE-US enhanced late phase vascular imaging. This is an important finding as the persistence of a hypoechoic liver lesion in to the late phase of CE-US imaging is typical of a colorectal liver metastasis and an agent that optimises the late phase would allow improved characterisation of colorectal liver metastases. As a result, CE-US was then compared to percutaneous unenhanced ultrasound and found to have improved sensitivity and accuracy in the detection of colorectal liver metastases (sensitivity 100%, accuracy 90.8% versus 64.4% and 64.4% respectively). Furthermore, the optimal late phase imaging was achieved by the lowest dose of agent (0.4mL) that would allow repeated injections if incorporated into routine clinical practice. These findings support the growing evidence base for percutaneous CE-US and it is likely that CE-US will replace unenhanced ultrasound in routine clinical practice. (Abstract shortened by ProQuest.)

Treatment and survival of patients with metastatic upper gastrointestinal cancer : hard to digest?

The thesis presents an analysis of population-based trends in incidence, treatment and overall survival in patients diagnosed with tumors along the upper gastrointestinal tract, with a special focus on metastasized disease. The four anatomical subsites discussed in detail are the esophagus, stomach, pancreas and small intestine. In this thesis we also investigated if there was a interhospital variation in the prescription of palliative chemotherapy, among patients with metastatic gastric and pancreatic cancer diagnosed in ten community hospitals in the South of the Netherlands. Furthermore, we investigated the influence of incidence and treatment volume on the outcome of patients with metastatic pancreatic cancer

Diagnosis and treatment of pituitary tumours: a starting-point for manipulation of cancer with hypothalamic hormones

In order to make a well-founded choice between the therapeutic modalities presently available it is important to have a clear picture of the differences in the natural history of the various types of pituitary tumours. One of the most important questions regards possible differences in the tendency of the various tumours to grow extrasellarly. A related question concerns the relationship between the secretion rate of growth hormone, prolactin etc. and the size of the respective tumour. In other words: do high serum levels of these hormones in general indicate the presence of a large tumour and do moderately increased levels point to a smaller tumour? A parallel and for the management sometimes crucial question is a possible relationship between tumour growth rate and the age of the patient. Furthermore, one can ask what - in a therapeutic sense - may be the significance of a combined secretion of growth hormone and prolactin by a pituitary tumour. The therapeutic part of our study concerns the efficacy and the rapidity, with which the desired therapeutic endpoint may be reached by means of (transsphenoidal) surgery, irradiation or the combination of these treatments in the various types of pituitary tumours. Furthermore, we have considered the value of medical treatment as an additional or - possibly - as primary therapy