scholarly journals Paraneoplastische dermatomyositis bij rectumcarcinoom: belang van snelle diagnose en therapie, maar onduidelijkheid over de beste aanpak

2021 ◽  
Author(s):  
P. LEMMENS ◽  
G. MERTENS ◽  
L. MORTIER ◽  
L. VAN OVERBEKE ◽  
F. VANHOENACKER
Keyword(s):  
Rectal Cancer ◽  
Autoimmune Disease ◽  
Paraneoplastic Syndrome ◽  
Treatment Options ◽  
Rectal Adenocarcinoma ◽  
Rapid Diagnosis ◽  
Adequate Treatment ◽  
Fast Recognition ◽  
Biochemistry Test ◽  
Systemic Manifestations

Paraneoplastic dermatomyositis in rectal cancer: importance of rapid diagnosis and therapy, but uncertainty about the best approach A 55-year-old woman, recently diagnosed with peritoneal metastasized rectal adenocarcinoma, developed a rash on her face, hands and torso, shortly after starting chemotherapy, as well as progressive proximal myalgia. Based on the typical symptoms, the increased creatine kinases (CK) levels after a biochemistry test and the characteristic abnormalities after an EMG, the diagnosis of dermatomyositis was made. Dermatomyositis (DM) is a rare autoimmune disease characterized by inflammation of the skin and muscles, which may also be accompanied by systemic manifestations. The etiology of dermatomyositis is still not fully understood. When dermatomyositis develops at older age, however, it is often a paraneoplastic syndrome. DM is a disease that can have a rapid and severe course. Thereby, fast recognition and adequate treatment are extremely important. The symptoms, diagnosis and treatment options are discussed in the article on the basis of the current literature.

scholarly journals Choroidal Metastasis as the Initial Presentation of Rectal Adenocarcinoma

2021 ◽  
Author(s):  
FNU Amisha ◽  
Tanvi Harishbhai Patel ◽  
Shubham Biyani ◽  
Prachi Saluja ◽  
Nitesh Gautam ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Lung Metastasis ◽  
Vision Loss ◽  
Treatment Options ◽  
Rectal Adenocarcinoma ◽  
Unknown Primary ◽  
Evidence Based ◽  
Rare Occurrence ◽  
Choroidal Metastasis ◽  
Evidence Based Treatment

Choroidal metastasis from rectal cancer is a rare occurrence with limited literature on appropriate evidence-based treatment options. We describe the case of 44-year-old man who presented with left-sided painful vision loss who was found to have left choroidal and multiple lung metastasis from an unknown primary which was later found to be rectal adenocarcinoma.

A multicenter phase Ib/II study of DNA-PK inhibitor peposertib (M3814) in combination with capecitabine and radiotherapy in patients with locally advanced rectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS144-TPS144
Author(s):  
Paul Bernard Romesser ◽  
Emma B. Holliday ◽  
Tony Philip ◽  
Rocio Garcia-Carbonero ◽  
Jaume Capdevila ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib

TPS144 Background: Perioperative radiotherapy and chemotherapy, followed by total mesorectal excision, is the standard of care for patients with locally advanced rectal cancer (LARC). However, 1/3 of these patients still develop distant metastases, indicating the need for more effective therapies. In addition, strategies that increase pathological complete response rates are needed to enable non-surgical management of LARC. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway for double-strand break repair. Peposertib (M3814), a potent, selective, orally administered DNA-PK inhibitor, has been shown to potentiate the effect of ionizing radiation in a human colon cancer xenograft model and several colon cancer cell lines. Peposertib is being investigated in several different trials across multiple indications. This Phase Ib/II study (NCT03770689) aims to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of the neoadjuvant treatment combination of peposertib, capecitabine, and radiotherapy (RT) in patients with LARC. Methods: Patients aged ≥18 years with histologically confirmed and resectable Stage II/III rectal adenocarcinoma are eligible. Induction chemotherapy is permitted, but residual disease must first be documented by MRI, digital rectal examination and endoscopy. Patients who received other anticancer therapies or those with prior pelvic RT are excluded. At open-label Phase Ib (open), 18–30 patients (n = 3 per cohort) will receive peposertib + capecitabine (orally, 825 mg/m2 twice daily [BID]) + RT (45–50.4 Gy), 5 days/week. Peposertib 50 mg once daily (QD) was the starting dose. Additional dose levels will range between 100─800 mg QD. Dose escalation is determined by the safety monitoring committee and guided by a Bayesian 2-parameter logistic regression model. At Phase II (planned), 150 patients will be randomized (1:1) to receive oral capecitabine (825 mg/m2 BID) + RT (45–50 Gy), with either oral peposertib (recommended phase II dose [RP2D] or placebo, QD for 5 days/week. Primary objectives are to define a maximum tolerated dose and RP2D (Phase Ib), and to evaluate the efficacy of peposertib + capecitabine + RT in terms of pathological/clinical complete response (Phase II). Secondary objectives include assessment of antitumor activity (Phase Ib), quality of life outcomes (Phase II), and PK of peposertib, and the safety and tolerability of the combination therapy (both phases). To date, one patient has received peposertib 50 mg QD, six patients peposertib 100 mg QD, three patients peposertib 150 mg QD, and three patients peposertib 250 mg QD. Clinical trial information: NCT03770689.

Hip Cartilage Restoration: Available Evidence and Current Trends

2018 ◽  
Vol 02 (02) ◽  
pp. 081-087
Author(s):  
Tyler Collins
Keyword(s):  
Autologous Chondrocyte Implantation ◽  
Treatment Options ◽  
Cost Effective ◽  
Nonoperative Treatment ◽  
Current Evidence ◽  
Adequate Treatment ◽  
Cartilage Lesions ◽  
Chondrocyte Implantation ◽  
Osteochondral Grafting ◽  
Autologous Chondrocyte

AbstractTreatment of cartilage pathology is controversial. In the hip, it is even more so as identification and treatment of early cartilage disease are relatively new and little evidence exists. With the advent and more widespread use of hip arthroscopy, easier access to the hip joint is available, and adequate treatment is possible with less morbidity. Many treatment options exist for cartilage lesions including nonoperative treatment, debridement, microfracture, acetabuloplasty, cartilage fixation, cartilage scaffolds, autologous chondrocyte implantation, and osteochondral grafting. While far from definitive, the current evidence suggests that smaller cartilage lesions (< 4 cm2) have good results with most treatments while larger lesions fare better with treatments that produce hyaline-like cartilage. The most cost-effective arthroscopic treatments of smaller cartilage lesions include acetabuloplasty and microfracture, while larger lesions should be considered for autologous matrix-induced chondrogenesis or matrix-assisted autologous chondrocyte implantation. Larger cartilage lesions with bone disease are more adequately treated with open procedures such as osteochondral grafting or total hip arthroplasty.

CCTG CO.28 primary endpoint analysis: Neoadjuvant chemotherapy, excision and observation for early rectal cancer, the NEO trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3508-3508
Author(s):  
Hagen Fritz Kennecke ◽  
Carl J Brown ◽  
Jonathan M. Loree ◽  
Husein Moloo ◽  
Derek J. Jonker ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
High Risk ◽  
Tumor Progression ◽  
Primary Endpoint ◽  
Organ Preservation ◽  
Rectal Adenocarcinoma ◽  
The United States ◽  
High Rate ◽  
Pelvic Mri ◽  
Preservation Rate

3508 Background: CO.28 (NCT03259035) is a phase II study designed to determine if patients with cT1-T3a/bN0 rectal cancer can be treated with induction chemotherapy (FOLFOX/CAPOX) and organ-preserving surgery. Methods: Patients with MRI staged cT1-3a/bN0 tumors and no pathologic (p) high risk features received 6/4 cycles of FOLFOX/CAPOX, repeat sigmoidoscopy/pelvic MRI and subsequent Transanal Endoscopic Surgery (TES) in the absence of tumor progression. ypT0/T1N0 tumors were treated with observation while ypT2+ or ypN+ stage were recommended Total Mesorectal Excision (TME). The primary endpoint was protocol specified Organ Preservation Rate (psOPR = ypT0/T1N0, no p high risk features) and actual Organ Preservation Rate (aOPR = ypT0/T1N0 stage plus higher yp stage patients who declined TME surgery). The study would be considered negative with an psOPR of 50% or lower (H0) and as promising if it is 65% or higher (H1). Results: Between 08/2017 to 05/2020, 58 eligible patients were accrued in Canada and the United States, median age was 67 years, 71% male. All had well-moderately differentiated, non-mucinous rectal adenocarcinoma and median tumor height was 6 cm (range 0-18). Median follow-up was 15.4 months. Chemotherapy with FOLFOX (32) or CAPOX (26) was administered, 90% completed all planned cycles. A total of 56/58 (97%) proceeded to TES, while one patient was ineligible due to tumor progression (1.7%) and one declined. In the intention to treat analysis, the psOPR was 57% (95% CI 43-70%) while the aOPR was 79% (95% CI 67% to 89%) due to 13/23 declining recommended TME surgery. Of 10 patients who proceeded to recommended TME, a complete R0 TME was performed in 9/10, and no p residual carcinoma was found in 7/10. Crude loco-regional (LR) and distant recurrence rates were 3.5% (95% CI 0.4 to 12%) and 0%, respectively. A recurrence occurred in 1/13 patients who initially declined TME surgery. Conclusions: In select patients with early stage rectal cancer, three months of induction CAPOX/FOLFOX followed by TES resulted in a high OPR without the use of pelvic irradiation. The observed high rate of pathologic downstaging may point to high chemo-responsiveness in early rectal adenocarcinoma with no p high risk features. Further trials to evaluate this approach are justified and updated results will be presented. Clinical trial information: NCT03259035. [Table: see text]

scholarly journals SPAR – a randomised, placebo-controlled phase II trial of simvastatin in addition to standard chemotherapy and radiation in preoperative treatment for rectal cancer: an AGITG clinical trial

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Michael B. Jameson ◽  
Kirsten Gormly ◽  
David Espinoza ◽  
Wendy Hague ◽  
Gholamreza Asghari ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Prognostic Score ◽  
Prognostic Significance ◽  
Rectal Adenocarcinoma ◽  
Trial Registration ◽  
Tumour Regression ◽  
Preoperative Treatment ◽  
Ordered Categories ◽  
Pelvic Mri ◽  
Link Type

Abstract Background Retrospective studies show improved outcomes in colorectal cancer patients if taking statins, including overall survival, pathological response of rectal cancer to preoperative chemoradiotherapy (pCRT), and reduced acute and late toxicities of pelvic radiation. Major tumour regression following pCRT has strong prognostic significance and can be assessed in vivo using MRI-based tumour regression grading (mrTRG) or after surgery using pathological TRG (pathTRG). Methods A double-blind phase 2 trial will randomise 222 patients planned to receive long-course fluoropyrimidine-based pCRT for rectal adenocarcinoma at 18+ sites in New Zealand and Australia. Patients will receive simvastatin 40 mg or placebo daily for 90 days starting 1 week prior to standard pCRT. Pelvic MRI 6 weeks after pCRT will assess mrTRG grading prior to surgery. The primary objective is rates of favourable (grades 1–2) mrTRG following pCRT with simvastatin compared to placebo, considering mrTRG in 4 ordered categories (1, 2, 3, 4–5). Secondary objectives include comparison of: rates of favourable pathTRG in resected tumours; incidence of toxicity; compliance with intended pCRT and trial medication; proportion of patients undergoing surgical resection; cancer outcomes and pathological scores for radiation colitis. Tertiary objectives include: association between mrTRG and pathTRG grouping; inter-observer agreement on mrTRG scoring and pathTRG scoring; studies of T-cell infiltrates in diagnostic biopsies and irradiated resected normal and malignant tissue; and the effect of simvastatin on markers of systemic inflammation (modified Glasgow prognostic score and the neutrophil-lymphocyte ratio). Trial recruitment commenced April 2018. Discussion When completed this study will be able to observe meaningful differences in measurable tumour outcome parameters and/or toxicity from simvastatin. A positive result will require a larger RCT to confirm and validate the merit of statins in the preoperative management of rectal cancer. Such a finding could also lead to studies of statins in conjunction with chemoradiation in a range of other malignancies, as well as further exploration of possible mechanisms of action and interaction of statins with both radiation and chemotherapy. The translational substudies undertaken with this trial will provisionally explore some of these possible mechanisms, and the tissue and data can be made available for further investigations. Trial registration ANZ Clinical Trials Register ACTRN12617001087347. (www.anzctr.org.au, registered 26/7/2017) Protocol Version: 1.1 (June 2017).

Addition of Oxaliplatin to Continuous Fluorouracil, l-Folinic Acid, and Concomitant Radiotherapy in Rectal Cancer: The Lyon R 97-03 Phase I Trial

2001 ◽  
Vol 19 (9) ◽  
pp. 2433-2438 ◽  
Author(s):  
Gilles Freyer ◽  
Nadine Bossard ◽  
Pascale Romestaing ◽  
Françoise Mornex ◽  
Olivier Chapet ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Phase I ◽  
Folinic Acid ◽  
Dose Level ◽  
Dose Escalation ◽  
Local Treatment ◽  
Rectal Adenocarcinoma ◽  
Severe Diarrhea ◽  
Phase Ii Studies ◽  
Level 1

PURPOSE: Oxaliplatin could increase the efficacy of fluorouracil (5-FU)/folinic acid chemoradiotherapy in rectal cancer. We tested three dose levels to identify a feasible oxaliplatin dose for combination therapy. PATIENTS AND METHODS: Between February 1998 and April 2000, we included 17 rectal adenocarcinoma patients in a single-center phase I study. Patients had T4 rectal carcinoma, T1-T3 disease with colostomy refusal, or potentially operable T2/T3 M1 requiring local treatment. Pelvic radiotherapy was 45 Gy over 5 weeks, 1.8 Gy/fraction, with concomitant chemotherapy weeks 1 and 5. Chemotherapy was oxaliplatin 80, 100, or 130 mg/m2 2-hour infusion on day 1 followed by l-folinic acid 100 mg/m2/d intravenous bolus, and 5-FU 350 mg/m2/d continuous infusion on days 1 to 5 (FolfoR1). Six patients refusing surgery received additional contact radiotherapy +/− brachytherapy. Dose escalation proceeded if less than two of six patients had dose-limiting toxicity (DLT) at a given dose-level. RESULTS: All except two patients completed treatment; patients at level 1 (prolonged grade 1 thrombocytopenia) and level 3 (prolonged cold-related dysesthesia) had no second chemotherapy course. Median follow-up is 14 months (range, 2 to 28 months). One elderly patient at dose level 1 had DLT asthenia, severe diarrhea and vomiting, and more than 10% weight loss. There were no other DLTs and no severe rectitis or gastrointestinal toxicity. There were objective responses at all doses and no progressions. Eight patients underwent radical surgery after chemoradiotherapy. Two had complete pathologic responses. CONCLUSION: FolfoR1 seems feasible and effective. Dose escalation did not increase toxicity. Although the MTD was not reached in this study, we recommend oxaliplatin 130 mg/m2 for phase II studies because it is the dose determined from studies in metastatic patients with no toxicity when given concurrently with radiation.

Surgical treatment options for rectal cancer

2004 ◽  
pp. 155-237
Author(s):  
G. A. Santoro ◽  
G. Di Falco ◽  
M. Trompetto ◽  
C. O. Finne ◽  
C. Pastore ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Surgical Treatment ◽  
Treatment Options

scholarly journals Management of Rectal Cancer and Liver Metastatic Disease: Which Comes First?

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Georgios Tsoulfas ◽  
Manousos-Georgios Pramateftakis
Keyword(s):  
Rectal Cancer ◽  
Metastatic Disease ◽  
Treatment Options ◽  
Surgical Techniques ◽  
Hepatic Metastases ◽  
Multimodality Treatment ◽  
Cancer Management ◽  
Metastatic Lesions ◽  
Synchronous Resection ◽  
Multimodality Approach

In the last few decades there have been significant changes in the approach to rectal cancer management. A multimodality approach and advanced surgical techniques have led to an expansion of the treatment of metastatic disease, with improved survival. Hepatic metastases are present at one point or another in about 50% of patients with colorectal cancer, with surgical resection being the only chance for cure. As the use of multimodality treatment has allowed the tackling of more complicated cases, one of the main questions that remain unanswered is the management of patients with synchronous rectal cancer and hepatic metastatic lesions. The question is one of priority, with all possible options being explored. Specifically, these include the simultaneous rectal cancer and hepatic metastases resection, the rectal cancer followed by chemotherapy and then by the liver resection, and finally the “liver-first” option. This paper will review the three treatment options and attempt to dissect the indications for each. In addition, the role of laparoscopy in the synchronous resection of rectal cancer and hepatic metastases will be reviewed in order to identify future trends.

Phase III Trial of Fluorouracil-Based Chemotherapy Regimens Plus Radiotherapy in Postoperative Adjuvant Rectal Cancer: GI INT 0144

2006 ◽  
Vol 24 (22) ◽  
pp. 3542-3547 ◽  
Author(s):  
Stephen R. Smalley ◽  
Jacqueline K. Benedetti ◽  
Stephen K. Williamson ◽  
John M. Robertson ◽  
Norman C. Estes ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Anterior Resection ◽  
Rectal Adenocarcinoma ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Adjuvant Chemoradiotherapy ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Locoregional Failure ◽  
Before And After

Purpose Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens. Patients and Methods After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m2/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT). Patients were stratified by operation type, T and N stage, and time from surgery. Results Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 49% to 55% of the bolus arms versus 4% in the PVI arm. No disease-free survival (DFS) or OS difference was detected (3-year DFS, 67% to 69% and 3-year OS, 81% to 83% in all arms). Locoregional failure (LRF) at first relapse was 8% in arm 1, 4.6% in arm 2, and 7% in arm 3. LRF in T1-2, N1-2, and T3, N0-2 primaries who received low anterior resection (those most suitable for primary resection) was 5% in arm 1, 3% in arm 2, and 5% in arm 3. Conclusion All arms provide similar relapse-free survival and OS, with different toxicity profiles and central catheter requirements. LRF with postoperative therapy is low, justifying initial resection for T1-2, N0-2 and T3, and N0-2 anterior resection candidates.

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