A clinical study of metastasized rectal cancer treatment: assessing a multimodal approach

Abstract Metastasized rectal cancer has long been considered incurable. During recent years, the treatment of rectal cancer patients has been improved, and nowadays, a subgroup of patients might even be cured. The aim of this study was to investigate the optimal timing of treatment in a multimodal therapy schedule in order to see whether the addition of bevacizumab (Avastin) to conventional chemotherapy was effective. The study included 39 patients with metastatic rectal cancer between 2009 and 2011, and three were excluded due to the lack of metastases or lack of follow-up information. The remaining 36 patients were divided into groups by treatment intention. The group with curative intention received mainly oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months followed by preoperative radiotherapy (RT) and surgery. Palliative patients had very different treatments depending on their needs of palliation. The median survival time for patients with curative intention was 31 months and for the palliative patients 12 months. Four of the patients (11 %) with curative intention were considered cured at the end of follow-up. The response to chemotherapy after 2-month treatment is a good prognostic sign for which patients can be cured. Long-lasting palliation can be obtained with this treatment schedule. The main side effects were gastrointestinal events, including bowel perforation, neuropathy, thrombo-embolic disease and reduced general condition. All side effects are known, and the treatment is considered tolerable. We conclude that a good treatment schedule would be oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months, followed by preoperative RT and surgery

PINCH is an independent prognostic factor in rectal cancer patients without preoperative radiotherapy - a study in a Swedish rectal cancer trial of preoperative radiotherapy

<p>Abstract</p> <p>Background</p> <p>The clinical significance between particularly interesting new cysteine-histidine rich protein (PINCH) expression and radiotherapy (RT) in tumours is not known. In this study, the expression of PINCH and its relationship to RT, clinical, pathological and biological factors were studied in rectal cancer patients.</p> <p>Methods</p> <p>PINCH expression determined by immunohistochemistry was analysed at the invasive margin and inner tumour area in 137 primary rectal adenocarcinomas (72 cases without RT and 65 cases with RT). PINCH expression in colon fibroblast cell line (CCD-18 Co) was determined by western blot.</p> <p>Results</p> <p>In patients without RT, strong PINCH expression at the invasive margin of primary tumours was related to worse survival, compared to patients with weak expression, independent of TNM stage and differentiation (<it>P </it>= 0.03). No survival relationship in patients with RT was observed (<it>P </it>= 0.64). Comparing the non-RT with RT subgroup, there was no difference in PINCH expression in primary tumours (invasive margin (<it>P </it>= 0.68)/inner tumour area (<it>P </it>= 0.49). In patients with RT, strong PINCH expression was related to a higher grade of LVD (lymphatic vessel density) (<it>P </it>= 0.01)</p> <p>Conclusions</p> <p>PINCH expression at the invasive margin was an independent prognostic factor in patients without RT. RT does not seem to directly affect the PINCH expression.</p

Biological and histological factors as predictors in rectal cancer patients : A study in a clinical trial of preoperative radiotherapy

With improved surgical techniques and preoperative radiotherapy (RT) the local recurrence rate in rectal cancer patients has been reduced, however the mortality rate is still high and there is a huge variation in the response to preoperative RT in patients with the same tumour stage. To improve patient’s survival, it is of great importance to identify good prognostic and predictive factors that help us to select the best suited patients for preoperative RT in the future. For many years, studies of neoplastic transformation have mainly focused on tumour cells. In recent years, researchers have realised that the stroma around tumour cells and their extracellular matrix components also play an important role in tumour carcinogensesis. The aim of this thesis was to investigate the biological factors, survivin and particularly interesting new cysteine-histidine rich protein (PINCH), histological factors, inflammatory infiltration, fibrosis, necrosis, mucinous content, angiogenesis and lymphangiogenesis as well as their relationships to preoperative RT and to clinical variables in rectal cancer patients who participated in a Swedish rectal cancer trial of preoperative RT. In paper I, the expression of survivin and its relationship to preoperative RT and clinical factors were investigated in 98 primary rectal tumours and adjacent normal mucosa. In all patients, positive survivin expression was independently related to worse survival compared to negative survivin expression in a multivariate analysis. In paper II, PINCH expression and its relationship to RT, clinical, histological and biological factors were investigated at the invasive margin and inner tumour area in 137 primary rectal tumours and in cell line of fibroblasts. In patients without RT, strong PINCH expression was independently related to worse survival in a multivariate analysis. No survival relationship was found in the patients with RT, and there was no difference in PINCH expression between the subgroups of non-RT and RT at the invasive margin/inner tumour area. In patients with RT, strong PINCH expression at the inner tumour area was related to a high level of lymphatic vessel density (LVD). In paper III, the frequency of LVD/blood vessel density (BVD) was analysed at the periphery, the inner tumour area and the invasive margin of 138/140 primary rectal tumours and correlated to RT, clinical, histological and biological factors. In all patients, LVD at the periphery of the tumour was independently related to better survival compared to LVD at the inner tumour area/invasive margin. In all patients, a higher LVD at the periphery was related to negative (wild type) p53 expression. In paper IV, the inflammatory infiltration, fibrosis, necrosis and mucinous content were studied in relation to RT, clinical and biological parameters in preoperative biopsies (n = 153) and in primary tumours (n = 148). In all patients and in the subgroups of non-RT and RT a higher grade of inflammatory infiltration was independently related to improved survival compared to weak inflammatory infiltration in a multivariate analysis. In this thesis, survivin, PINCH, LVD and inflammatory infiltration are independent prognostic factors in rectal cancer patients who participated in a clinical trial of preoperative RT. This information may help us to improve patient’s survival by selecting the best suited patients for preoperative RT in the future

Linköping University Medical Dissertations

Biological and histological factors as predictors in rectal cancer patients – A study in a clinical trial of preoperative radiotherap

Anniskelulainsäädännön muutoksen vaikutukset Pirkanmaan alueen ravintoloissa : Yrittäjien sekä ravintoloitsijoiden kokemuksien perusteella

Tämän opinnäytetyön tarkoituksena oli kerätä Pirkanmaan seudun ravintoloitsijoiden sekä yrittäjien kokemuksia ja henkilökohtaisia mielipiteitä uudistuneesta alkoholilainsäädännöstä, joka tuli voimaan 1.3.2018. Aikaisempia tutkimuksia aiheesta ei ollut tehty, joten tutkimus oli erittäin ajankohtainen. Työn toimeksiantajana toimivat Pirkanmaan matkailu- ja ravintolapalveluiden yrittäjät ry eli MaRa MRY. Toimeksiantaja valittiin siten, että työntekijät sekä toimeksiantaja hyötyivät toistensa tuesta sekä tuloksista mitä saatiin. Työn tavoitteena oli kerätä laaja-alaisesti erilaisia kokemuksia ja mielipiteitä sekä uudistuneen lainsäädännön tuomia muutoksia käytännön tasolla. Työn teoriaosuudet käsittelivät uudistunutta anniskelulainsäädäntöä, ravintolakulttuuria sekä laadullista tutkimusta. Tutkimus toteutettiin haastattelemalla 12:sta ravintoloitsijaa sekä yrittäjää Tampereen seudun ruokaravintoloista, pubeista ja yökerhoista. Haastattelut toteutettiin teemahaastatteluin ja haastateltavien anonymiteetti säilytettiin. Haastattelukysymyksiä oli 15 ja haastattelut äänitettiin, jonka jälkeen ne litteroitiin ja väri koodattiin teemojen mukaan. Haastateltavat ottivat alkuun uuden alkoholilainsäädännön hieman skeptisesti vastaan. Kuitenkin tutkimustuloksista voidaan todeta, että uudistus loi jännittyneitä, mutta iloisia tunteita. Kaikki vastaajat olivat sitä mieltä, että oli jo aikakin muutokselle, sillä moni vastaajista piti vanhaa alkoholilakia rajoittavana ja vanhanaikaisena. Haastatteluissa yhtenä tärkeimpänä asiana ilmeni, että uudistunut alkoholilaki ei ollut tuonut minkäänlaisia negatiivisia vaikutuksia mukanaan. Mielenkiintoisena huomiona todettiin, että suurin osa vastaajista oli sitä mieltä, ettei muutos vaikuta kauheasti heidän toimintatapoihin. Haastatteluista voitiin todeta, että Suomi on vihdoin pääsemässä muun maailman tasolle ja ehkä jonakin päivänä tulevaisuudessa myös meillä olisi toimiva alkoholilainsäädäntö, jossa ravintoloitsijoilla ja yrittäjillä olisi enemmän vapauksia toimia ilman suurempia rajoitteita. Uudistunut alkoholilainsäädäntö toteutettiin todella nopealla aikataululla, jonka takia mahdollisesti toteutus jäi hieman vajaaksi. Yrittäjät ja ravintoloitsijat jäivät kaipaamaan lisää, sillä uudistus rajoittaa vieläkin monen toimintaa, eikä tuonut toivomia vapautuksia. Kaiken myötä uudistus voitiin todeta silti hienoksi edistysaskeleeksi.The purpose of this thesis was to gather personal opinions and experiences of restaurateurs in the Pirkanmaa region concerning the amendment of the Alcohol Act that came into force partly on 1 January 2018, and in completeness on 1 March 2018. The study was commissioned by the Finnish Hospitality Association MaRa of Tampere. The main goal of the study was to gather a wide variety of different experiences and opinions regarding the changes the revised legislation caused in practice.   The theoretical parts of the study deal with the revised Alcohol Act, restaurant culture in general, and qualitative research. The study was conducted by interviewing 12 restaurateurs and entrepreneurs of restaurants, pubs and night clubs in the Tampere region. The interviews, which consisted of 15 questions, were conducted as focused interviews and the anonymity of the interviewees was maintained. The interviews were recorded, and transcribed and color coded by theme afterwards.  Overall, the interviewees were quite skeptical about the new legislation, although the majority were happy and enthusiastic about it. All of the interviewees thought that it was about time for a change because many of them considered the old Alcohol Act as restrictive and outdated. It was also interesting to notice that most of the interviewees thought that the changes have very little effect on their practices. It can be noticed from the interviews that Finland is finally reaching the same level with the rest of the world and perhaps someday in the future we can have a functional Alcohol Act, too

Mucinous and Non-Mucinous Rectal Adenocarcinoma - Differences in Treatment Response to Preoperative Radiotherapy

There is a need to personalize the treatment for rectal cancer patients. The aim of this study was to analyze therapy response and prognosis after preoperative radiotherapy in rectal cancer patients with mucinous adenocarcinoma compared to those with non-mucinous adenocarcinoma. The study included retrospectively collected data from 433 patients, diagnosed with rectal cancer in the South East health care region in Sweden between 2004 and 2012. Patients with non-mucinous adenocarcinoma that received short-course radiotherapy before surgery had better overall survival, cancer specific survival, and disease-free survival, as well as distant- and local-recurrence-free survival (p = 0.003, p = 0.001, p = 0.002, p = 0.002, and p = 0.033, respectively) compared to the patients that received long-course radiotherapy with concomitant capecitabine. The results were still significant after adjusting for sex, age, stage, differentiation, and chemotherapy in the neoadjuvant and/or adjuvant setting, except for local-recurrence-free survival that was trending towards significance (p = 0.070). In patients with mucinous adenocarcinoma, no difference in survival was seen when comparing patients that had short-course radiotherapy and patients that had long-course radiotherapy. However, none of 18 patients with mucinous adenocarcinoma treated with long-course radiotherapy had local tumor progression, compared to 7% of 67 patients with non-mucinous adenocarcinoma. The results indicate that mucinous adenocarcinoma and non-mucinous adenocarcinoma may respond differently to radiotherapy.Funding Agencies|Swedish Cancer Foundation [CAN 2016/341]; Liu Cancer Network [200331]; Foundation of the Department in Oncology in Linkopings Research Fund [06000896]; Region Ostergotland, Sweden [06000933]</p

Age as a potential predictor of acute side effects during chemoradiotherapy in primary cervical cancer patients

Background Toxicity during chemoradiotherapy (CRT) in cervical cancer patients might limit the chances of receiving an optimal treatment and to be cured. Few studies have shown relationships between acute side effects and patients age. Here, the association between age and acute side effects such as nausea/vomiting, diarrhea and weight loss during CRT was analysed in cervical cancer patients. Methods This study included 93 patients with primary cervical cancer stage IBI to IVA who received CRT from 2013 to 2019. The frequency of symptoms/toxicity grade was analysed by using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Results Patients ≥ 52 years had a significantly higher frequency of nausea/vomiting and increased grade  ≥ 3 toxicity during CRT compared to younger patients (p&lt;0.001, p = 0.001). Toxicity grade ≥ 3 of nausea/vomiting was associated with increased frequency of weight loss (p = 0.001), reduced ADL (p = 0.001) and dose modifications of both radiotherapy (RT) (p = 0.020) and chemotherapy (CT) (p = 0.030) compared to toxicity grade 2. The frequency of diarrhea (p = 0.015) and weight loss (p = 0.020) was higher in older patients compared to younger. Conclusions Older patients have an increased risk of acute side effects as nausea/vomiting, diarrhea and weight loss. Age could be useful in predicting acute side effects in primary cervical cancer patients with CRT.Funding Agencies: Linköping University</p

Low-dose capecitabine (Xeloda) for treatment for gastrointestinal cancer

The prodrug capecitabine (Xeloda) has been an important drug for treatment for gastrointestinal cancer (GI-cancer). This study explores the efficacy of continuous metronomic Xeloda, as well as tolerability and best response during treatment. Patients (n=35) with stage IV GI-cancer were included in the study and were divided into two groups; upper (n=13) and lower (n=22) GI-cancer. All patients were given continuous metronomic Xeloda (500 mg×2). Best response was measured by radiological and clinical examination including laboratory results. Standard RECIST criteria were used. Median age was 66 (range 29-86). Those patients who received first and second line had the longest duration of treatment. For patients with metastatic gastrointestinal cancer, metronomic capecitabine (Xeloda) may be beneficial both as far as tumor control and quality of life is concerned. In this pilot study, palliation for more than 2 years is observed for 6 of the 35 patients

A clinical study of metastasized rectal cancer treatment : assessing a multimodal approach

Metastasized rectal cancer has long been considered incurable. During recent years, the treatment of rectal cancer patients has been improved, and nowadays, a subgroup of patients might even be cured. The aim of this study was to investigate the optimal timing of treatment in a multimodal therapy schedule in order to see whether the addition of bevacizumab (Avastin) to conventional chemotherapy was effective. The study included 39 patients with metastatic rectal cancer between 2009 and 2011, and three were excluded due to the lack of metastases or lack of follow-up information. The remaining 36 patients were divided into groups by treatment intention. The group with curative intention received mainly oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months followed by preoperative radiotherapy (RT) and surgery. Palliative patients had very different treatments depending on their needs of palliation. The median survival time for patients with curative intention was 31 months and for the palliative patients 12 months. Four of the patients (11%) with curative intention were considered cured at the end of follow-up. The response to chemotherapy after 2-month treatment is a good prognostic sign for which patients can be cured. Long-lasting palliation can be obtained with this treatment schedule. The main side effects were gastrointestinal events, including bowel perforation, neuropathy, thrombo-embolic disease and reduced general condition. All side effects are known, and the treatment is considered tolerable. We conclude that a good treatment schedule would be oxaliplatin (Eloxatin) in combination with capecitabine (Xeloda) with or without bevacizumab (Avastin) for 2 months, followed by preoperative RT and surgery