Down-staging depth score to predict outcomes in locally advanced rectal cancer achieving ypl stage after neoadjuvant chemo-radiotherapy versus de novo stage pl cohort:A propensity score-matched analysis

Objective：Prognosis of patients with locally advanced rectal cancer（LARC）but achieving yp T1–2N0 stage after neoadjuvant concurrent chemo-radiotherapy（CRT）has been shown to be favorable.This study aims to determine whether the long-term outcome of yp T1–2N0 cases can be comparable to that of p T1–2N0 cohort that received definitive surgery for early disease.Method：From January 2008 to December 2013,449 consecutive patients with rectal cancer were treated and their outcome maintained in a database.Patients with LARC underwent total mesorectal excision（TME）surgery at4–8 weeks after completion of CRT,and those achieving stage yp I were identified as a group.As a comparison,stage p I group pertains to patients whose initially limited disease was not upstaged after TME surgery alone.After propensity score matching（PSM）,comparisons of local regional control（LC）,distant metastasis-free survival（DMFS）,disease-free survival（DFS）and overall survival（OS）were performed using Kaplan-Meier analysis and log-rank test between yp I and p I groups.Down-staging depth score（DDS）,a novel method of evaluating CRT response,was used for subset analysis.Results：Of the 449 patients,168 matched cases were generated for analysis.Five-year LC,DMFS,DFS and OS for stage p I vs.yp I groups were 96.7%vs.96.4%（P=0.796）,92.7%vs.73.6%（P=0.025）,91.2%vs.73.6%（P=0.080）and 93.1%vs.72.3%（P=0.040）,respectively.In the DDS-favorable subset of the yp I group,LC,DMFS,DFS and OS resulted in no significant differences in comparison with the p I group（P=0.384,0.368,0.277 and0.458,respectively）.Conclusions：LC was comparable in both groups;however,distant metastasis developed more frequently in down-staged LARC than de novo early stage cases,reflecting the need to improve the efficacy of systemic treatment despite excellent pathologic response.DDS can be an indicator to identify a subset of the yp I group whose longterm oncologic outcomes are as good as those of stage p I cohort.

Feasibility and oncological outcomes of laparoscopic rectal resection following neo-adjuvant chemo-radiotherapy: A systematic review

AIM: To study the feasibility and oncological outcomesfollowing laparoscopic total mesorectal excision(LTME) in patients who have received Neo-adjuvant long course chemo-radiotherapy(LCRT). METHODS: A protocol driven systematic review of published literature was undertaken to assess the feasibility and oncological outcomes following LTME in patients receiving LCRT. The feasibility was assessed using peri-operative outcomes and short term results. The oncological outcomes were assessed using local recurrence, disease free survival and overall survival.RESULTS: Only 8 studies-1 randomized controlled trial, 4 Case Matched/Controlled Studies and 3 Case Series were identified matching the search criteria. The conversion rate was low(1.2% to 28.1%), anastomotic leak rates were similar to open total mesorectal excision(0%-4.1% vs 0%-8.3%). Only 3 studies reported on local recurrence rates(5.2%-7.6%) at median 34 mo follow-up. A single study described disease free survival and overall survival at 3 years as 78.8% and 92.1% respectively. CONCLUSION: LTME following LCRT is feasible in experienced hands, with acceptable short term surgical outcomes and with the usual benefits associated with minimally invasive procedures. The long term oncological outcomes of LTME after LCRT appear to be comparable to open procedures but need further investigation.

Tumor acid microenvironment-activated self-targeting&splitting gold nanoassembly for tumor chemo-radiotherapy

Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy.Herein,a pH-responsive gold nanoassembly is designed to overcome these problems.Polyethylene glycol linked raltitrexed(RTX,target ligand and chemotherapy drug)and two tertiary amine molecules(1-(2-aminoethyl)pyrrolidine and N,N-dibutylethylenediamine)are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX).The Au-NNP(RTX)nanoassembly could remain at about 160 nm at the blood circulation(pH 7.4),while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH(pH 6.8).This pH-responsive disassembly behavior endows Au-NNP(RTX)better tumor tissue permeability through the better diffusion brought by the size reduction.Meanwhile,after disassembly,more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability.Most importantly,the results show that Au-NNP(RTX)possesses of high tumor accumulation and effective tumor penetration,thereby enhancing the tumor chemo-radiotherapy efficiency.

Evolving treatment strategies for colorectal cancer: A critical review of current therapeutic options

Management of rectal cancer has markedly evolved over the last two decades.New technologies of staging have allowed a more precise definition of tumor extension.Refinements in surgical concepts and techniques have resulted in higher rates of sphincter preservation and better functional outcome for patients with this malignancy.Although,preoperative chemoradiotherapy followed by total mesorectal excision has become the standard of care for locally advanced tumors,many controversial matters in management of rectal cancer still need to be defined.These include the feasibility of a non-surgical approach after a favorable response to neoadjuvant therapy,the ideal margins of surgical resection for sphincter preservation and the adequacy of minimally invasive techniques of tumor resection.In this article,after an extensive search in PubMed and Embase databases,we critically review the current strategies and the most debatable matters in treatment of rectal cancer.

Treatment strategy for colorectal cancer with resectable synchronous liver metastases:Is any evidence-based strategy possible?

Fifteen percent to twenty-five percent of patients affected by colorectal cancer presents with liver metastases at diagnosis. In resectable cases, surgery is the only potentially curative treatment and achieves survival rates up to 50% at 5 years. Management is complex, as colorectal resection, liver resection, chemotherapy, and, in locally advanced mid/low rectal tumors, radiotherapy have to be integrated. Modern medical practice usually relies on evidence-based protocols. Levels of evidence for synchronous metastases are poor:published studies include few recent prospective series and several retrospective analyses collecting a limited number of patients across long periods of time. Data are difficult to be generalized and are mainly representative of single centre's experience, biased by local recruitment, indications and surgical technique. In this context, surgeons have to renounce to "evidence-based medicine" and to adopt a sort of "experience-based medicine". Anyway, some suggestions are possible. Simultaneous colorectal and liver resection can be safely performed whenever minor hepatectomies are planned, while a case-by-case evaluation is mandatory in case of more complex procedures. Neoadjuvant chemotherapy is preferentially scheduled for patients with advanced metastatic tumors to assess disease biology and to control lesions. It can be safely performed with primarytumor in situ , even planning simultaneous resection at its end. Locally advanced mid/low rectal tumor represents a further indication to neoadjuvant therapies, even if treatment's schedule is not yet standardized. In summary, several issues have to be solved, but every single HPB centre should define its proper strategy to optimize patient's selection, disease control and safety and completeness of surgery.

Capecitabine for locally advanced and metastatic colorectal cancer:A review

Capecitabine (Xeloda) is an oral fluoropyrimidine which is produced as a pro-drug of fluorouracil, and shows improved tolerability and intratumor drug concentrations following its tumor-specif ic conversion to the active drug. We have searched the Pubmed and Cochrane databases from 1980 to 2009 with the purpose of reviewing all available information on Capecitabine, focusing on its clinical effectiveness against colorectal cancer. Special attention has been paid to trials that compared Capecitabine with standard folinic acid (leucovorin, LV)-modulated intravenous 5-fluorouracil (5-FU) bolus regimens in patients with metastatic colorectal cancer. Moreover the efficacy of Capecitabine on metastatic colorectal cancer, either alone or in various combinations with other active drugs such as Irinotecan and Oxaliplatin was also assessed. Finally, neoadjuvant therapy con- sisting of Capecitabine plus radiation therapy, for locally advanced rectal cancer was analysed. This combination of chemotherapy and radiotherapy has a special role in tumor down staging and in sphincter preservation for lower rectal tumors. Comparative trials have shown that Capecitabine is at least equivalent to the standard LV-5-FU combination in relation to progression-free and overall survival whilst showing a better tolerability prof ile with a much lower incidence of stomatitis. It is now known that Capecitabine can be combined with other active drugs such as Irinotecan and Oxaliplatin. The combination of Oxaliplatin with Capecitabine represents a new standard of care for metastatic colorectal cancer. Combinating the Capecitabine-Oxaliplatin regimen with promising new biological drugs such as Bevacizumab seems to give a realistic prospect of further improvement in time to progression of metastatic disease. Moreover, preoperative chemo-radiation using oral capecitabine is better tolerated than bolus 5-FU and is more effective in the promotion of both down-staging and sphincter preservation in patients with locally advanced rectal cancer. Finally, the outcomes of recently published trials suggest that capecitabine seems to be more cost effective than other standard treatments for the management of patients with colorectal cancer.

Survival and Prognostic Factors in Patients with Carcinoma of Cervical Stump

Purpose: To evaluate patients with carcinoma of cervical stump (CCS) and analyse different clinico-pathologic factors affect prognosis. Patients and Methods: This study was carried out through review of clinical records of patients. Recorded data included information on age, tumor stage, presenting symptoms, size of tumor, histopathology, grade, type, cause of subtotal hysterectomy (STH), treatment and follow-up results. Staging according to International Federation of Gynecology and Obstetrics (FIGO) staging system was done through: PHYSICAL examination, pelvic examination under anaesthesia, chest X-ray, magnetic resonance imaging (MRI) of the abdomen and pelvis, cystoscopy, rectosigmoidoscopy and intravenous pyelography. Prognostic factors as age, size of tumor, stage, lymph node (LN) involvement, pathological type, grade and type of CCS either true or coincidental were analysed through multivariate analysis. Results: 62% of patients are above 50 years with stage II in 48.7%. Squamous cell carcinoma was more common but 54% are of GIII. 89% were true CCS. Positive lymph nodes were reported in 27%. The predominant reason for STH was abnormal bleeding (73%). In about 95% of cases, women seeked medical attention because of symptoms and the most common presenting symptom was bleeding (54%). According to the stage and performance status of patients, treatment consisted of radiotherapy either external or interstitial, chemotherapy and chemoradiotherapy. Through multivariate analysis, the following was found to have adverse impact on survival: Coincidental type (P = 0.04), high grade (P = 0.03), advanced stage (P = 0.01), larger tumor size (P = 0.02), lymph node involvement (P = 0.029) and older age (P = 0.035). While pathological type was not (P = 0.52). After median follow-up of 52 months;5-year overall survival was 65%. Conclusion: CCS has a low morbidity. Adverse survival outcomes can be anticipated in those patients with: high grade lesions, advanced stages, large tumor size, coincidental type, older age and positive lymph node involvement.

Clinical observation of platinum-based combined with concurrent three-dimensional conformal radiotherapy in patients with locally advanced non-small cell lung cancer

Objective： The aim of our study was to explore the shortterm efficacy of platinumbased combined with concur rent chemoradiotherapy for locally advanced nonsmallcell lung cancer （NSCLC）. Methods： Between 2006 to 2010, 78 cases of locally advanced NSCLC were enrolled into this trial. All patients were given platinumbased chemotherapy combined with concurrent threedimensional conformal radiotherapy （3DCRT）. Chest CT scans were obtained during endexpiratory and endinspiratory pauses when performing positioning. Image fusion was done after the image data was transferred to treat ment plan system （TPS）. The target volume was delineated on the fusion images. The chemotherapy was given on the first day of radiotherapy. Comprehensive examinations were conducted 46 weeks after concurrent chemoradiotherapy to assess shortterm efficacy. Results： Complete remission （CR） was achieved in 8 cases and partial remission （PR） in 54 cases. The efficiency rate reached 79.5%. Grade IllIV radiation esophagitis occurred in 11.5%. No exit and death cases during treat ment. Conclusion： Concurrent chemoradiotherapy could significantly improve the shortterm efficacy and prolong survival of stage III NSCLC, meanwhile the adverse reactions could be tolerated.

A Clinic-Epidemilogical Study of Cases of Locally Advanced Non Small Cell Lung Cancer (NSCLC) That Received Radiotherapy at NCI Cairo in the Period from 2001-2010

Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for local control and their effect on overall survival (OAS). Materials and Methods: This is a retrospective study including 121 patients with primary locally advanced NSCLC diagnosed between 2001 and 2010 at the radiotherapy department , National Cancer Institute, Cairo University, Egypt. Results: The study showed significant correlation between the tumor size 60, moderately differentiated tumors G2 and treatment outcomes;better locoregional control and better survival rates. On the opposite side poorly differentiated tumors G3, tumor size > 7 cm had the worst locoregional control and survival rates. The study also showed significant statistical correlation between treatment modality, locoregional control and survival rates. Patients who were treated by either concommitent chemo-radiotherapy or sequential chemo-radiotherapy had better local control compared to other patients who were treated by radical radiotherapy, and they also had the best survival rates among all the other treatment groups. The average 6 months OAS rates for all studied patients were 60.3% while 12 months survival rates were 38.8%. The median OAS was 7 months. Conclusions: From the present study, we concluded that concomitant chemo-radiotherapy is the treatment of choice for locally advanced non small cell lung cancer;also we concluded that better performance status and higher hemoglobin levels have better treatment outcome in these cases.

Prognostic Factors and Treatment Outcome in 178 Locally Advanced Cervical Cancer Patients

Background: To evaluate local control, survival, radiation side effects and treatment outcome in locally advanced cervical cancer patients. Materials and Methods: Among 2006-2011, 178 patients with locally advanced cervical cancer were treated with chemoradiotherapy +/-?radiotherapy and high dose rate (HDR) brachytherapy. Follow-up was complete for all patients. Concomitant chemotherapy was not administered in 44 patients due to renal impairments and ECOG of 2 - 3. Results: The median follow-up period was 34.5 months (range, 5 to 93) and 42 months (range, 14 to 93 months) for alive patients. Five years local-regional control, progression-free survival and overall survival rates were 87.8%, 58.9% and 67.3% in all patients, respectively. In this retrospective study young age, tumor diameter, stage, presence of residual tumor and administration of chemotherapy were effected in survival analysis. The parameters which affected the complete response of patients were defined as presence of concomitant chemotherapy and number of courses <5. Central region recurrence rate was defined higher in the group with treatment duration of 9 weeks and higher (p = 0.044). Conclusion: Primary chemoradiotherapy +/-?radiotherapy achieved a satisfactory rate of local control and survival rates with acceptable complications in locally advanced cervical cancer. Concomitant chemotherapy and treatment duration were the important prognostic factors for completed response locally advanced cervical cancers.