PURPOSE: Erlotinib-gemcitabine combined chemotherapy is considered as the standard treatment for unresectable pancreatic cancer. This study aimed to determine the clinical factors associated with response to this treatment. MATERIALS AND METHODS: This retrospective study included 180 patients with unresectable pancreatic cancer who received ≥2 cycles of gemcitabine-erlotinib combination therapy as first-line palliative chemotherapy between 2006 and 2014. "Long-term response" was defined as tumor stabilization after >6 chemotherapy cycles. RESULTS: The median progression-free survival (PFS) and overall survival (OS) were 3.9 and 8.1 months, respectively. On univariate analysis, liver metastasis (p=0.023) was negatively correlated with long-term response. Locally advanced stage (p=0.017), a history of statin treatment (p=0.01), and carcinoembryonic antigen levels <4.5 (p=0.029) had a favorable effect on long-term response. On multivariate analysis, a history of statin treatment was the only independent favorable factor for long-term response (p=0.017). Prognostic factors for OS and PFS were significantly correlated with liver metastasis (p=0.031 and 0.013, respectively). A history of statin treatment was also significantly associated with OS after adjusting for all potential confounders (hazard ratio, 0.48; 95% confidence interval, 0.26-0.92; p=0.026). CONCLUSION: These results suggest that statins have a favorable effect on "long-term response" to gemcitabine-erlotinib chemotherapy in unresectable pancreatic cancer patients. Statins may have a chemoadjuvant role in stabilizing long-term tumor growth.
Adenocarcinoma/*drug therapy/secondary ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Deoxycytidine/administration & dosage/analogs & derivatives ; Disease-Free Survival ; Erlotinib Hydrochloride/administration & dosage ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Male ; Middle Aged ; Neoplasm Staging ; Pancreatic Neoplasms/*drug therapy/pathology ; Retrospective Studies ; Survival Rate ; Young Adult

OBJECTIVETo explore the feasibility, safety and efficacy of intraoperative regional infusion chemotherapy by celiac trunk in advanced gastric cancer patients.

METHODSOne hundred and twenty-six patients with advanced gastric cancer(stageII(-III() were screened from database of Gastrointestinal Surgery Department of Taizhou People's Hospital between January 2008 and December 2010 who underwent R0 resection and D2 lymphadenectomy, received postoperative chemotherapy(XELOX or FOLFOX), and had complete follow-up data. They were divided into infusion chemotherapy group (65 cases) and control group (61 cases) according to regional infusion chemotherapy or not (fluorine 1 000 mg and cisplatin 60 mg). The side effects of chemotherapy, parameters related to the operation, long-term survival and relapse rate were compared between the two groups.

RESULTSThe baseline data between the two groups were comparable(all P>0.05). Postoperative III( and IIII( adverse reaction of chemotherapy was not significantly different between the two groups (P>0.05). The time of postoperative intestinal function recovery [(67.9±14.8) hours vs. (68.9±15.0) hours, t=-0.380, P=0.705), volume of postoperative 1-week drainage [(66.1±17.1) ml vs.(61.9±18.2) ml, t=1.478, P=0.142], recent morbidity of complications[55.4%(36/65) vs. 49.2%(30/61), χ=0.256, P=0.613], and the long-term morbidity of complications [16.9% (11/65) vs. 14.8% (9/61), χ=0.111, P=0.739] were all not significantly different between the two groups. The 3-year survival rate and 3-year relapse-free survival rate in infusion chemotherapy group were significantly higher than those in control group(58.4% vs. 37.7%, χ=5.382, P=0.020; 58.4% vs. 34.4%, χ=6.636, P=0.010).

CONCLUSIONRegional infusion chemotherapy by celiac trunk during operation for advanced gastric cancer patients is safe and feasible, and can reduce the risk of local recurrence and improve survival rate.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Celiac Artery ; Chemotherapy, Cancer, Regional Perfusion ; adverse effects ; methods ; mortality ; Cisplatin ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Fluorine ; administration & dosage ; adverse effects ; therapeutic use ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Gastrectomy ; Humans ; Leucovorin ; therapeutic use ; Lymph Node Excision ; Neoplasm Recurrence, Local ; prevention & control ; Organoplatinum Compounds ; therapeutic use ; Postoperative Complications ; Recovery of Function ; Stomach Neoplasms ; drug therapy ; mortality ; surgery ; Survival Rate

OBJECTIVETo evaluate the efficacy and safety of gemcitabine combined with ifosfamide (GI regimen)in patients with recurrent or metastatic nasopharyngeal carcinoma after failure of platinum-based chemotherapy.

METHODSThe clinical data of 27 nasopharyngeal carcinoma patients, who received GI regimen between April 2005 and March 2014 after failure of prior platinum-based chemotherapy, were retrospectively reviewed,and relevant prognostic factors were explored.

RESULTSAll patients were evaluable for efficacy and toxicity. No patient achieved complete response (CR). Partial response (PR) was achieved in ten patients, stable disease (SD) in thirteen patients, progressive disease (PD) in four patients, with a response rate of 37.0% and an overall disease control rate (PR+SD) of 85.2%. For ten PR patients, the median duration of response was 5.5 months. The median progression-free survival of the whole group was 6.7 months, and the Kaplan-Meier estimate of median overall survival was 17.4 months. The 1-year survival rate was 72.6%. Toxicity was mainly hematological: Grade III or IV anemia, neutropenia and thrombocytopenia were found in 3.7%, 37.0% and 18.5% of all patients, respectively. Univariate and multivariate analyses indicated that dose intensity of gemcitabine was a significant prognostic factor for PFS, whereas salvage treatment after failure of GI regimen was a significant prognostic factor for OS.

CONCLUSIONSGemcitabine and ifosfamide combination is effective and well tolerated by patients with advanced nasopharyngeal carcinoma pretreated with platinum-based chemotherapy. Further clinical study is warranted.

Anemia ; chemically induced ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Disease-Free Survival ; Humans ; Ifosfamide ; administration & dosage ; adverse effects ; Induction Chemotherapy ; Kaplan-Meier Estimate ; Nasopharyngeal Neoplasms ; drug therapy ; mortality ; pathology ; Neutropenia ; chemically induced ; Platinum ; therapeutic use ; Remission Induction ; Salvage Therapy ; Survival Rate ; Thrombocytopenia ; chemically induced ; Treatment Failure

OBJECTIVETo evaluate the safety and efficacy of gemcitabine combined with S-1 in the treatment of advanced pancreatic cancer.

METHODSA retrospective analysis of the clinical data of 49 patients with advanced pancreatic cancer, who did not receive radiotherapy and chemotherapy, were divided into two groups: the study group (25 cases), and control group (24 cases). Patients in the study group received gemcitabine 1 000 mg/m² via intravenous drip at the first and 8th days, and received S-1 80 mg/m², morning and evening (twice a day) for the first 14 days, and 21 days as a treatment cycle of chemotherapy.The control group was given GEMOX regimen: Gemcitabine 1 000 mg/m² via intravenous drip at the first and 8 days, and oxaliplatin 130 mg/m² via intravenous drip at the first day, and 21 d for a treatment cycle of chemotherapy. The efficacy and adverse reactions in patients of the study and control groups were observed and compared.

RESULTSThe efficiency of the study group was 32.0% and disease control rate was 72.0%. The efficiency of the control group was 25.0% and disease control rate was 58.3%. The differences between the two groups were statistically not significant (P > 0.05 for all). The clinical benefit rate in the study group and control group were 80.0% and 50.0%, respectively, showing a significant difference (P < 0.05). The median survival time was 9.7 months in patients of the study group and 9.0 months in the control group, with a significant difference (P < 0.05). The drug toxicity was well tolerated in both groups, and no chemotherapy-related death occurred. The major adverse reactions were myelosuppression and digestive tract reactions, and the adverse reactions in the study group were lower than those in the control group.

CONCLUSIONSGemcitabine combined with S-1 is effective and safe in the treatment of advanced pancreatic cancer, with less side effects, and can be tolerated by the patients.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; adverse effects ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Drug Administration Schedule ; Drug Combinations ; Humans ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Oxonic Acid ; administration & dosage ; adverse effects ; Pancreatic Neoplasms ; drug therapy ; pathology ; Retrospective Studies ; Tegafur ; administration & dosage ; adverse effects

BACKGROUNDSystemic chemotherapy (SC) is the recommended treatment for gastric cancer with liver metastasis. However, the improvement in survival has been disappointing. The aim of this study was to compare the therapeutic efficacy of gastrectomy with transarterial chemoembolization plus SC (GTC) and SC alone for gastric cancer with synchronous liver metastasis.

METHODSFrom January 2008 to December 2013, 107 gastric cancer patients with synchronous liver metastasis attending the four participating centers were enrolled in this multicenter, ambispective, controlled cohort study. Patients who underwent GTC (n = 32) were compared with controls who were received SC alone (n = 75). The primary endpoints of the study were overall survival (OS) and progression-free survival (PFS). The secondary endpoints were response rate to treatment and treatment-related adverse effects.

RESULTSThe median OS was 14.0 months (95% confidence interval [CI ]: 13.1-14.9 months) in the GTC treatment group and 8.0 months (95% CI : 6.6-9.4 months) in SC group, this difference being statistically significant (P < 0.001). The median PFS was significantly longer in the GTC than in the SC group (5 months, 95% CI : 2.2-7.8 months vs. 3 months, 95% CI : 2.3-3.4 months, respectively) (P < 0.001). The rate of response to treatment was significantly better in the GTC than the SC group (59.4% vs. 37.4%, respectively) (P = 0.035). According to multivariate analysis, OS in patients receiving combination treatment was significantly correlated with the size (P = 0.037) and extent of liver metastases (P < 0.001). PFS was also correlated with the extent of liver metastases (P = 0.003).

CONCLUSIONSGTC is more effective than SC alone in patients with gastric cancer with synchronous liver metastasis. GTC therapy prolongs the survival of selected gastric cancer patients with synchronous liver metastasis.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Chemoembolization, Therapeutic ; methods ; Cohort Studies ; Combined Modality Therapy ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Gastrectomy ; Humans ; Liver Neoplasms ; secondary ; Male ; Middle Aged ; Stomach Neoplasms ; pathology ; therapy

OBJECTIVETo evaluate the efficacy and safety of fixed dose rate (FDR) gemcitabine infusion in combination with docetaxel in patients with relapsed/refractory soft tissue sarcoma.

METHODSClinicopathological data of 28 patients with relapsed/refractory soft tissue sarcoma treated in our hospital from April 2008 to August 2013 were reviewed in this study. The patients received 900 mg/m² gemcitabine with a FDR infusion (10 mg/m²/min) in a total dose of 900 mg/m² on days 1 and 8, and 75 mg/m² docetaxel intravenously over 60 min on day 8 of a 21-day cycle. When irradiation was conducted before drug therapy, the dose of gemcitabine was reduced to 675 mg/m² on days 1 and 8. The clinicopathological characteristics, short-term response, long-term survival status and toxicity were analyzed retrospectively.

RESULTSThe 28 patients received a total of 118 cycles of therapy (range 1-8 cycles, median 4 cycles per patient). No patient achieved complete response (CR), 4 partial responses (PR) and 11 stable diseases (SD), with an overall response rate (ORR) of 14.3% and clinical benefit rate (CBR) of 53.6%. The median progression-free survival (PFS) was 3.2 months and the median overall survival (OS) was 8.5 months. PFS and OS were correlated with the response to this treatment regimen (P < 0.0001). Patients with clinical benefit had significantly better PFS and OS than the patients with progressive disease (P < 0.05 for all). The ORR, CBR, PFS and OS were better in patients with leiomyosarcoma than in patients with other histological subtypes in this study, but the differences were not significant (P > 0.05 for all). Grade 3-4 neutropenia, anemia and thrombocytopenia were 50.0%, 17.9% and 14.3%, respectively. Only one patient (3.6%) had febrile neutropenia. Grade 3 non-hematologic toxicities were nausea/vomiting (3.6%) and mucositis (3.6%). No grade 4 non-hematologic toxicities were observed. Almost all non-hematologic toxicities were grade 1-2 and manageable.

CONCLUSIONSThe fixed dose rate (FDR) gemcitabine infusion in combination with docetaxel is an effective treatment regimen for patients with relapsed/refractory soft tissue sarcoma, and with tolerable adverse reactions.

Antimetabolites, Antineoplastic ; administration & dosage ; therapeutic use ; Antineoplastic Agents ; administration & dosage ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Humans ; Leiomyosarcoma ; drug therapy ; Neoplasm Recurrence, Local ; drug therapy ; Neutropenia ; Retrospective Studies ; Sarcoma ; drug therapy ; Taxoids ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVEThe aim of this study was to explore the effect of SPARC on the anti-cancer effect of gemcitabine and underlying mechanism in pancreatic cancer.

METHODSAfter treating with gemcitabine, the proliferation rate of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells was detected by MTT assay. The cell cycle distribution and cell apoptosis in each group were examined by flow cytometry, and the capability of clone formation was tested by adhesion-dependent clone formation assay. The apoptosis-related proteins were analyzed by Western blot.

RESULTSThe growth of pancreatic cancer cells was inhibited by gemcitabine in a time-dependent and dose-dependent manner. Its IC50 at 24, 48, and 72-h was (40.1 ± 2.5) µmol/L, (15.0 ± 0.5) µmol/L and (6.6 ± 0.1) µmol/L, respectively. The overexpression of SPARC increased the inhibitory effect of gemcitabine on growth of pancreatic cancer MIA PaCa2/SPARC69 cells, presenting a dose- and time- dependent manner. Its IC50 at 24, 48, 72 h was (24.3 ± 1.5) µmol/L, (7.7 ± 0.3) µmol/L and (4.8 ± 0.2) µmol/L, respectively. The clone formation assay showed that before gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (2350 ± 125), (2130 ± 120) and (1567 ± 11), respectively. After gemcitabine treatment, the clone numbers of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were ( 1674 ± 79) , (1587 ± 94) and (557 ± 61), respectively. The overexpression of SPARC enhanced the chemosensitivity of MIA PaCa2 cells to gemcitabine chemotherapy. After treating with 10 µmol/L gemcitabine for 48 h, the ratio of G0/G1 cells in MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (56.0 ± 5.5)%, (55.0 ± 4.5)% and (68.0 ± 7.0)%, respectively. The cells arrested at G0/G1 phase were significantly increased in the MIA PaCa2/SPARC69 cells. The apoptosis rates of MIA PaCa2, MIA PaCa2/V and MIA PaCa2/SPARC69 cells were (22.4 ± 2.5)%, (19.9 ± 2.0)% and (37.7 ± 3.9)%, respectively, indicating that overexpression of SPARC enhanced the gemcitabine-induced apoptosis in MIA PaCa2 cells. The Western blot analysis showed that, compared with MIA PaCa2 and MIA PaCa2/V cells, the expression of caspase-2, -8, -9 and cleaved PARP protein was significantly increased, while the expression of Bcl-2 was not changed significantly in the MIA PaCa2/SPARC69 cells.

CONCLUSIONSPARC can enhance the chemosensitivity of pancreatic cancer cells to gemcitabine via regulating the expression of apoptosis-related proteins.

Antimetabolites, Antineoplastic ; administration & dosage ; pharmacology ; Apoptosis ; drug effects ; Caspase 2 ; metabolism ; Caspase 8 ; metabolism ; Caspase 9 ; metabolism ; Cell Cycle ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cysteine Endopeptidases ; metabolism ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; pharmacology ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Humans ; Osteonectin ; metabolism ; Pancreatic Neoplasms ; metabolism ; pathology ; Poly(ADP-ribose) Polymerases ; metabolism ; Time Factors

OBJECTIVEThe aim of this study was to analyze the clinical characteristics, treatment and prognosis of advanced urothelial carcinoma of the bladder (AUCB).

METHODSThe clinicopathological data of 117 patients with AUCB admitted in our hospital from 1998 to 2009 were reviewed. All patients received first-line chemotherapy. The survival rate was calculated by Kaplan-Meier analysis and log-rank test.

RESULTSThe median age of all patients was 56 years and the male-to-female ratio was 3.33:1. Their 6-, 12-, 24-, 36- and 60-month survival rates were 90.3%, 61.3%, 32.3%, 24.2% and 8.1%, respectively. In the first-line chemotherapy regimen, the effectiveness rate of gemcitabine + platinum drugs was 49.3% (37/75), the median progression-free survival(PFS) was 7.9 months and overall survival (OS) was 18.7 months. The effectiveness of cyclophosphamide + epirubicin + platinum drug regimen was 45.5% (10/22), Median PFS was 7.1 months and OS was 15.3 months. The effectiveness of paclitaxel + platinum drug regimen was 47.1% (8/17), median PFS was 6.5 months and OS was 13.7 months. Among them, the effectiveness rate of the gemcitabine + cisplatin regimen in 67 patients was 47.8%, the median PFS was 7.0 months and OS was 15.3 months. In the 13 patients who received paclitaxel + carboplatin regimen, the effectiveness rate was 53.8%, median PFS was 7.7 months and OS was 16.0 months. The major side effects were leucopenia and thrombocytopenia, mostly were tolerable, of grade I to II.

CONCLUSIONSIn advanced unresectable and metastatic urothelial carcinoma of the bladder, GC regimen is recognized as a standard first-line chemotherapy, with a higher effectiveness and tolerable side effects. Taxane and molecular targeted drugs may further improve the therapeutic effect of the treatment of advanced urothelial carcinomas of the bladder in the future.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bone Neoplasms ; drug therapy ; secondary ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Transitional Cell ; drug therapy ; pathology ; secondary ; Cisplatin ; administration & dosage ; adverse effects ; Cyclophosphamide ; administration & dosage ; adverse effects ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; Disease-Free Survival ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Paclitaxel ; administration & dosage ; adverse effects ; Retrospective Studies ; Survival Rate ; Thrombocytopenia ; chemically induced ; Urinary Bladder Neoplasms ; drug therapy ; pathology ; Urothelium ; pathology

BACKGROUND/AIMS: Patients with cholangiocarcinoma usually present at an advanced stage, and more than 50% of cases are not resectable at the time of diagnosis. Recently, photodynamic therapy (PDT) has been proposed as a palliative and neoadjuvant modality. We evaluated whether combination of PDT and chemotherapy is more effective than PDT alone. METHODS: In total, 161 patients with cholangiocarcinoma diagnosed between February 1999 and September 2009 were evaluated. Sixteen patients were treated with PDT and chemotherapy (group A), and 58 were treated with PDT (group B). RESULTS: The median survival was 538 days (95% confidence interval [CI], 475.3 to 600.7) in group A and 334 days (95% CI, 252.5 to 415.5) in group B (p=0.05). Lymph node metastasis status, serum bilirubin of pretreatment, tumor node metastasis stage, treatment method (PDT with chemotherapy vs PDT alone), time to PDT and the number of PDT sessions were prognostic factors with statistical significance in the univariate analysis. A multivariate analysis showed that PDT with chemotherapy and more than two sessions of PDT were significant independent predictors of longer survival in advanced cholangiocarcinoma (hazard ratio [HR], 2.23; 95% CI, 1.18 to 4.20; p=0.013 vs HR, 1.79; 95% CI, 1.044 to 3.083; p=0.034). CONCLUSIONS: PDT with chemotherapy results in longer survival than PDT alone.
Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Bile Duct Neoplasms/*drug therapy ; *Bile Ducts, Intrahepatic ; Cholangiocarcinoma/*drug therapy/mortality ; Cholangiopancreatography, Endoscopic Retrograde ; Cisplatin/administration & dosage ; Combined Modality Therapy/mortality ; Deoxycytidine/administration & dosage/analogs & derivatives ; Female ; Fluorouracil/administration & dosage ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Photochemotherapy/*methods/mortality ; Treatment Outcome

OBJECTIVETo investigate the feasibility of Xelox(capecitabine plus oxaliplatin) in the volumetric modulated arc therapy(VMAT)-based preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer(LARC).

METHODSClinical data of 141 LARC patients in our hospital from April 2011 to April 2013 treated by preoperative CRT based on VMAT with concurrent Xelox followed by surgery were analyzed retrospectively. There were 95 men and 46 women, and the median age was 56 years old. Clinical staging was stage II( in 33 cases(18 cases with II(a, 11 cases with II(b, 4 cases with II(c) and stage III( in 108 cases(1 case with III(a, 52 cases with III(b, 55 cases with III(c). The target doses were 50 Gy for PTV1 in 25 fractions and 46 Gy for PTV2 in 23 fractions.

RESULTSAll the patients completed the planned radiotherapy, and only 2 cases were interrupted with acute grade 3 diarrhea. The overall incidence of grade 3 hematologic and non-hematologic adverse events during CRT was 9.9% and 16.3% respectively without grade 4 toxicity. Operation was performed after a median interval of 54 days(34-86 days) following CRT. The R0 resection rate was 100%, sphincter preservation rate for low rectal cancer was 45.8%(33/72), postoperative complication morbidity was 17.0%(24/141), pCR rate was 32.6%(46/141), and rates of pathological down-staging for the primary tumor, lymph node and clinical stage were 87.2%, 88% and 90.1%, respectively.

CONCLUSIONSXelox is feasible and well tolerated in the treatment of VMAT-based preoperative CRT for patients with LARC, with excellent rates of pCR and pathological down-staging.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Capecitabine ; Chemoradiotherapy ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Feasibility Studies ; Female ; Fluorouracil ; administration & dosage ; analogs & derivatives ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Organoplatinum Compounds ; administration & dosage ; Radiotherapy, Intensity-Modulated ; Rectal Neoplasms ; pathology ; therapy ; Treatment Outcome