Adjuvant Chemotherapy Group Research Articles

Application observation of neoadjuvant chemotherapy in radical resection of cervical cancer of stage IB2-IIB

Objective To investigate the efficacy of neoadjuvant chemotherapy combined with radical resection of cervical cancer in the treatment of stage IB2-ⅡB cervical cancer. Methods According to the treatment plan from October 2012 to October 2016 in the People′s Hospital of Luohu District of Shenzhen in 80 cases of stage IB2- II B cervical cancer patients were divided into observation group(n=43) and control group(n=37), the observation group was treated with neoadjuvant chemotherapy combined with radical surgery for cervical cancer, patients in the control group directly treated for radical resection of cervical cancer.Chemotherapy effect, operation time, intraoperative blood loss, postoperative pathological risk factor differences of two groups of patients were compared. Results (1)Evaluated the curative effect of neoadjuvant chemotherapy, squamous cell carcinoma group complete remission(CR) 4 cases, partial remission(PR) 22 cases, stable disease(SD), 6 cases of disease progression(PD) in 0 cases, in adenocarcinoma group CR 1 cases, PR 3 cases, SD 5 cases, PD 2 cases of squamous cell carcinoma group adjuvant chemotherapy was significantly better than that of adenocarcinoma group, the difference was statistically significant(z=2.4968, P=0.0063). (2)The operation time((215±57) min) and intraoperative blood loss((682±145) ml) in the observation group were significantly lower than those in the control group(((259±62) min, (758±193) ml)), the difference was statistically significant(t=3.8780, 2.2528, P=0.0002, 0.0263). (3)The two groups of patients with ureteral fistula(P=0.5039), vesicovaginal fistula(P=0.3639), wound healing(P=0.5182), lower extremity deep venous thrombosis(P=0.4818) complications had no significant difference.(4)The positive rate of the observation group of lymph nodes(χ2=8.2005, P=0.0000), parametrial infiltration rate(χ2=8.1553, P=0.0000) was significantly lower than the control group, the difference was statistically significant.Two groups of patients with deep myometrial invasion rate(χ2=0.0991, P=0.7516), the incidence of cancer embolus(χ2=0.0130, P=0.9176) compared to no statistical significance. Conclusion The effect of neoadjuvant chemotherapy on cervical squamous cell carcinoma is better than that of adenocarcinoma.Compared with the direct for radical resection of cervical cancer, neoadjuvant chemotherapy combined with radical resection of cervical cancer patients for the treatment of stage IB2-ⅡB cervical cancer, operation time and blood loss are lower, node positive and parametrial invasion and postoperative pathologic risk factors in lymph node also can get better effect. Key words: Neoadjuvant chemotherapy; Radical resection of cervical cancer; IB2-ⅡB stage; Cervical carcinoma; Squamous cell carcinoma; Adenocarcinoma

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate

BackgroundIn this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence.MethodsIn the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45–50.4 Gy in 25–28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1–14 and 22–35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included.ResultsBetween June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137–0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143–0.938, p = 0.036).ConclusionsIn pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Clinical Outcomes of Perioperative Chemotherapy in Patients With Locally Advanced Penile Squamous-Cell Carcinoma: Results of a Multicenter Analysis

The prognosis of patients with locally advanced penile squamous-cell carcinoma is primarily related to the extent of lymph node metastases. Surgery alone yields suboptimal results, and there is a paucity of data on these patients' outcomes. This retrospective study evaluated patients who received neoadjuvant or adjuvant chemotherapy from 1990 onward at 12 centers. Cox models were used to investigate prognostic factors for relapse-free survival and overall survival (OS). Among the 201 included patients, 39 (19.4%) had disease of T3-4 and N0 clinical stage; the remaining patients had clinical lymph node involvement (cN+). Ninety-four patients received neoadjuvant chemotherapy (group 1), 78 received adjuvant chemotherapy (group 2), and 21 received both (group 3). Eight patients for whom the timing of perioperative chemotherapy administration was unavailable were included in the Cox analyses. Forty-three patients (21.4%) received chemoradiation. Multivariate analysis for OS (n=172) revealed bilateral disease (P= .035) as a negative prognostic factor, while pelvic cN+ tended to be nonsignificantly associated with decreased OS (P= .076). One-year relapse-free survival was 35.6%, 60.6%, and 45.1% in the 3 groups, respectively. One-year OS was 61.3%, 82.2%, and 75%, respectively. No significant differences were seen on univariable analyses for OS between the groups (P= .45). Platinum type of chemotherapy and chemoradiation were not significantly associated with any outcome analyzed. Benchmark survival estimates for patients receiving perioperative chemotherapy for locally advanced penile squamous-cell carcinoma have been provided, with no substantial differences observed between neoadjuvant and adjuvant administration. This analysis may result in improved patient information, although prospective studies are warranted.

Adjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicentre randomised controlled trial

Aim of the studyPrevious results from our trial showed that adjuvant cisplatin and fluorouracil chemotherapy did not significantly improve survival after concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) at 2 years. Here, we present the data of long-term survival and late toxicities to further assess the ultimate therapeutic index of adjuvant chemotherapy (AC). MethodsPatients with stage III–IVB (except T3-4N0) NPC were randomly assigned to receive CCRT plus AC or CCRT only at seven institutions in China. Patients in both groups received cisplatin 40 mg/m2 weekly up to 7 weeks concurrently with radiotherapy. The CCRT plus AC group subsequently received adjuvant cisplatin 80 mg/m2 and fluorouracil 800 mg/m2/d for 120 h every 4 weeks for three cycles. The primary end-point was failure-free survival. ResultsTwo hundred and fifty-one patients were randomised to the CCRT plus AC group and 257 to the CCRT only group. After a median follow-up of 68.4 months, estimated 5-year failure-free survival rate was 75% in the CCRT plus AC group and 71% in the CCRT only group (hazard ratio 0.88, 95% confidence interval 0.64–1.22; p = 0.45). 66 (27%) of 249 patients in the CCRT plus AC group and 53 (21%) of 254 patients in the CCRT only group developed one or more late grade 3–4 toxicities (p = 0.14). ConclusionAdjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities. Registration numberNCT00677118.

Effectiveness of platinum-based adjuvant chemotherapy for muscle-invasive bladder cancer: A weighted propensity score analysis.

392 Background: The clinical evidence of adjuvant chemotherapy (AC ) is less robust than neoadjuvant chemotherapy (NAC). However, several surveys suggest that urologists prefer to use AC more frequently than NAC. We evaluate the clinical benefit of adjuvant platinum based chemotherapy following radical cystectomy (RC) for muscle-invasive bladder cancer (BCa) in routine clinical practice. Methods: This observational study was conducted to compare the effectiveness of AC versus observation postcystectomy in patients with clinicallymuscle-invasive BCa. Cancer-specific survival (CSS) and overall survival (OS) between the AC group and RC alone group were compared using Kaplan-Meiyer method and log-rank test. After adjusting for background factors using propensity score weighting, differences in CSS and OS between these two groups were compared. Subgroup analyses by the pathological characteristics were performed. Results: In total, 322 patients were included in this study. Of these, 23% received AC postcystectomy. Clinicopathological characteristics showed that patients in the AC group were pathologically more advanced and were at higher risk than the RC alone group. In the unadjusted population, although it is not significantly, the AC group had lower overall survival (3-years OS; 61.5% vs 73.6%, HR 1.44, p = 0.243, log-rank test, AC vs RC alone). In the weighted propensity score analysis, although it is not significantly, AC group were superior than RC alone groups (OS: HR 0.65, 95%CI 0.39-1.09, p = 0.099, log-rank test, AC vs RC alone). Subgroup analyses showed that AC significantly reduced the hazard ratio of OS and CSS in ≥ pT3, pN+, ly+, and v+ subgroups. Conclusions: The weighted propensity score analyses showed that platinum-based AC might be associated with increased CSS and OS in patients with high-risk invasive BCa.

Prognostic classification of muscle-invasive bladder cancer (MIBC) following radical cystectomy (RC) alone or with perioperative chemotherapy: Analysis of the U.S. National Cancer Database (NCDB).

372 Background: While the role of adjuvant therapy for MIBC is being evaluated in randomized trials of patients (pts) following RC with or without neoadjuvant chemotherapy (NC), pts receiving adjuvant chemotherapy (AC) have been excluded. Understanding the prognosis of a broad spectrum of pts undergoing RC with or without perioperative chemotherapy may aid patient selection, stratification and interpretation of nonrandomized data. We conducted a retrospective analysis of the NCDB to construct a comprehensive prognostic nomogram in this broad population. Methods: Data from NCDB was obtained for all patients diagnosed with clinical (c)-T2-T4aN0M0 urothelial carcinoma of bladder who underwent RC in the US from 2004-2013. Those who underwent RC > 6 months (mo) after initiating NC, received AC > 4 mo after RC were excluded to allow only those receiving optimal therapy. Pts with unknown race and number of lymph nodes (LNs) examined were also excluded. Multivariate analyses were conducted to determine the impact on survival of: clinical stage, pathologic (p)-stage, treatment group (RC alone, NC, AC), age, year of diagnosis, Charlson Comorbidity Index (CCI), race, number of examined LNs examined and sex. Results: A total of 10,256 pts were evaluable for analysis: 6864 in the RC group, 1380 in the AC group and 2012 in the NC group. On multivariate analysis, the following variables were significantly (p < 0.001) associated with survival: treatment group, age ( < 65 vs. ≥ 65 years), CCI, p-stage and number of examined LNs. Calibration was performed and the c-index was 0.79 (95% CI: 0.76-0.81). Limitations of a retrospective analysis apply. Conclusions: A comprehensive prognostic nomogram to predict the survival of pts with MIBC undergoing RC with or without NC or AC was proposed. The estimation of residual risk of mortality after RC alone or with AC or NC aids optimal stratification of pts in more inclusive randomized trials of subsequent adjuvant therapy. The nomogram also highlights the impact of comorbidities and age, and helps interpret non-randomized data evaluating perioperative regimens.

SMAD4 loss in colorectal cancer: Correlation with recurrence, chemoresistance, and immune infiltrate.

587 Background: Few markers reliably identify colorectal cancer (CRC) patients at risk of recurrence and death. SMAD4 loss occurs in 10-20% of cases and has shown promise in identifying high-risk stage II/III patients. We examined SMAD4 status and association with clinical/pathologic features in 446 stage I-IV CRC patients at Memorial Sloan Kettering (MSK). Methods: Patients undergoing curative resection were included (1981-2010). Familial polyposis syndrome patients and those with inadequate tissue were excluded. Tissue microarrays were constructed (n=364). Immunohistochemistry for SMAD4 and mismatch repair (MMR) proteins was completed. SMAD4 nuclear stain intensity was scored (scale=0-3; 0=loss). On whole sections, MMR proteins (present or absent), tumor-infiltrating lymphocytes (TILs) and peritumoral lymphocyte aggregates (PLAs) were scored (scale=0-3). Associations between clinical/pathologic features and SMAD4 loss vs. retention were analyzed. Kaplan-Meier estimates and log-rank test were used for recurrence-free and overall survival analyses (RFS and OS). Results: SMAD4 loss was noted in 13%. Median age at diagnosis was 53 years, and 51% were male. The cohort consisted of 61% hindgut tumors and 62% stage II/III patients. With up to 33 years of follow-up, the mean was 6 years. SMAD4 loss correlated with higher tumor and nodal stage, adjuvant therapy use, and lower TIL and PLA scores (p<0.04 for all). Unlike prior studies, no significant differences in OS based on SMAD4 status across the entire cohort were noted; however, older patients (>median) were noted to have worse OS with SMAD4 loss (p<0.01). SMAD4 loss did correlate with worse RFS (p=0.02), persisting even when excluding MMR-deficient patients. Additionally, SMAD4 loss was associated with worse RFS in both the adjuvant chemotherapy group (median RFS=3.8 vs. 13 years; p=0.06) and the resection-only group (median RFS=4.2 years vs. not yet reached; p< 0.01). Conclusions: SMAD4 loss correlates with worse RFS and resistance to adjuvant therapy. SMAD4 loss also correlates with lower TIL and PLA scores. Future work will address chemoresistance mechanisms, relevance to adjuvant therapy use, and loss of immune infiltrate in SMAD4-null tumors.

The Role of Adjuvant Chemotherapy for Colorectal Liver Metastasectomy after Pre-Operative Chemotherapy: Is the Treatment Worthwhile?

Peri-operative chemotherapy has been proposed to improve the survival of patients with colorectal cancer hepatic metastases (CRCHM). However, the role of the adjuvant chemotherapy post-metastasectomy for CRCHM patients who have undergone pre-operative chemotherapy is still undetermined. We retrospectively analyzed the role of adjuvant chemotherapy post-metastasectomy on relapse-free survival (RFS) and overall survival (OS) in 163 CRCHM patients who received pre-operative chemotherapy using a Kaplan-Meier curve and univariate/multiple Cox model. Ten patients with rapidly progressing disease were further excluded in a sensitivity analysis. Seven risk factors (metachronous/synchronous metastases, differentiated grade of the primary tumor, number of metastases, size of the max metastasis, duration of pre-operative chemotherapy, radiologic response and pathologic regression) were used to stratify patients and investigate the beneficial features of adjuvant chemotherapy post-metastasectomy. The results indicated that adjuvant chemotherapy post-metastasectomy prolonged both RFS (median RFS: 3.3 vs. 10.2 m, P = 0.002) and OS (median OS: 28.1 vs. 40.7 m, P = 0.005) in CRCHM patients who received pre-operative chemotherapy. After adjusting for other risk factors in a multiple Cox model, the adjuvant chemotherapy group was estimated to have a 54.0 % relapse-free survival (hazard ratio (HR) = 0.46, 95 % confidence interval (CI) 0.31 - 0.69, P < 0.001) and a 55.0 % overall survival (HR [95 % CI]: 0.45 [0.26 - 0.78], P = 0.005) advantage compared to patients without adjuvant chemotherapy. Additionally, the benefit of adjuvant chemotherapy post-liver resection remained in sensitivity analysis. After the risk stratification, patients with synchronous metastases, poor differentiation, ≥ 3 metastases per patient, size of the maximum metastasis >3 cm, a short duration of pre-operative chemotherapy, radiologic response and poor pathologic regression seem to benefit more from adjuvant chemotherapy. To sum up, adjuvant chemotherapy post-metastasectomy might be considered for CRCHM patients who have received preoperative chemotherapy, especially for those with high-risk factors.

Clinical Observation of Neoadjuvant Chemotherapy in High-Risk Stage II Colorectal Cancer: A Report of 24 Cases

Background: Neoadjuvant chemotherapy is the systemic chemotherapy before the start of local chemotherapy or radiotherapy. At present, neoadjuvant chemotherapy in the high-risk phase II (AJCC TNM stage II period, including T3N0M0 and T4N0M0) treatment of colon cancer reported less. The authors discussed the efficacy and safety of neoadjuvant chemotherapy in 24 patients with high-risk stage II colorectal cancer. Method: Forty-eight patients with stage II colorectal cancer were randomly divided into experimental group and control group, the postoperative complications, the side effects of chemotherapy drugs and the effect of chemotherapy drugs on the tumor were observed. The quality of life, survival time and tumor recurrence or metastasis was compared between the two groups. Result: 1) The incidence of complications in the neoadjuvant chemotherapy group was 20.8%, the incidence of adjuvant chemotherapy was 25%, and the overall complication rate was 22.9%. P values were greater than 0.05. 2) Through the comparison of the two groups of toxic and side effects, after SPASS software analysis, obtained P > 0.05, the two groups were not statistically significant. 3) After 3 - 4 courses of preoperative chemotherapy, CR (complete remission) and PD (disease progression) patients were 0 cases, PR (partial remission) was 11 (45.8%), NC/SD (no change) was 13 (54.2%). 4) Through the comparison of the quality of life of the two groups of patients, from the function, symptoms and the overall situation to statistics, P value 0.05, This comparison makes sense. 5) The 1-year survival rate was 100% (24/24) in the control group, with a 3-year survival rate of 92% (22/24) and a 5-year survival rate of 75% (9/12). All survival rates in the experimental group were 100% (24/24). 6) There were no recurrence or metastasis cases in the neoadjuvant chemotherapy group, and 2 cases of recurrence and 1 case of metastasis in the adjuvant chemotherapy group were compared with the recurrence or metastasis after tumor operation. The chi-square test is not statistically significant. Conclusion: Neoadjuvant chemotherapy plays a role in patients with high-risk second-stage colon cancer, the experimental group benefited significantly, especially in quality of life and survival time. At the same time, neoadjuvant chemotherapy is also a safe treatment.

Serial MRI Scan of Posterior Fossa Tumours Predict Patients at Risk of Developing Neurocognitive Impairment

Background:Brain tumours are the most common solid tumours in children. More than 50% of these tumours develop in the posterior cranial fossa. Long term survivors of posterior fossa tumours (PFT) suffer from neurocognitive and memory issues. We hypothesized that serial MRI scanning of brain would show differences in hippocampal and ACC volume change in PFT patients treated with and without chemo-radiotherapy.Material and Methods:Twelve patients (8 females and 4 males) underwent 76 serial MR imaging examinations before and during treatment for posterior fossa tumours. Seven patients (4 medulloblastoma, 2 as ependymoma and 1 high grade glioma) were treated with maximum surgical resection followed by adjuvant radiotherapy and chemotherapy (Group 1). The other five patients were diagnosed as pilocytic astrocytoma who were treated only with surgery (Group 2). Hippocampal volumes were obtained manually on high-resolution 3Tesla T1-weighted images and normalised to intracranial volume, while ACC thickness and volume were obtained automatically using FreeSurfer software.Results:After the treatment period, the change in normalised hippocampal volume from baseline was significantly lower in group 1 patients compared to group 2 (mean change -0.0001470 ± 8.981e-005; Mean ± SEM vs 0.0002765 ± 9.151e-005; Mean ± SEM, respectively, P=0.004). Displayed graphically, the negative hippocampal growth trajectory in group 1 gradually returned to a positive growth pattern. There were no statistically significant changes in ACC volume and thickness. Both groups had similar rates of pre-operative hydrocephalus.Conclusion:Compared to PFT patients treated with surgery alone, PFT patients treated with chemo-radiotherapy showed lower hippocampal volumes and altered hippocampal growth trajectory. Serial quantitative MRI measures of brain may provide a neuroanatomical substrate for assessing functional impact on normal brain function following treatment of posterior fossa tumours.

Outcomes of surveillance versus adjuvant chemotherapy for patients with stage IA and IB nonseminomatous testicular germ cell tumors.

Currently, it is accepted that risk assessment of clinical stage I (CS I) nonseminomatous germ cell tumors (NSGCT) patient is mainly dependent on the presence of lymphovascular invasion (LVI). Initial active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND) are acceptable treatment options for these patients, but there is no uniform consensus. The purpose of this study was to compare outcomes of active surveillance with adjuvant chemotherapy. A total of 201 patients with CS I NSGCT after orchiectomy were included. Outcomes of active surveillance and adjuvant chemotherapy were retrospectively analyzed. The prognostic significance of risk factors for survival and relapse was evaluated. Of the 201 patients, 110 (54.7%) received adjuvant chemotherapy, while the remaining 91 patients (45.3%) underwent surveillance. Relapses were significantly higher for patients underwent surveillance compared to adjuvant chemotherapy group (18.3 vs. 1.2%, p<0.001). The 5-year relapse-free survival (RFS) rate for patients who were treated with adjuvant chemotherapy was significantly better than those of patients underwent surveillance (97.6 vs. 80.8%, respectively; p<0.001). Univariate analysis showed that the presence of LVI (p=0.01) and treatment option (p<0.001) were prognostic factors for RFS and pT stage (p=0.004) and invasion of rete testis (p=0.004) and the presence of relapse (p<0.001) were significant prognostic factors for OS. Multivariate analysis revealed that the treatment strategy was an independent prognostic factor for RFS (p<0.001, HR 0.54). A logistic regression analysis demonstrated that treatment options (p=0.031), embryonal carcinoma (EC) >50% (p=0.013) and tumor diameter (p=0.016) were found to be independent factors for predicting relapse. Our results indicate that adjuvant chemotherapy is associated with improved RFS compared with surveillance for CS I NSGCT patients. Moreover, the treatment strategy is an important prognostic indicator for RFS and a predictive factor for relapse. Although adjuvant chemotherapy seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still preferred management option.

Epidemiology Data of Ovarian Cancer in Dr. Cipto Mangunkusumo Hospital, Jakarta

Objective: To describe the incidence of ovarian cancer and its characteristic&#x0D; in Dr. Cipto Mangunkusumo Hospital in the last 5 years.&#x0D; Method: This was cross sectional study design. The data was collected&#x0D; from Gynecology Oncology Division Cancer Registry and Dr.&#x0D; Cipto Mangunkusumo Hospital medical record from January 2009 to&#x0D; December 2013; follow up was performed to know the 4-years survival&#x0D; rate.&#x0D; Result: There were 98 subjects in this study. The majority incidence&#x0D; of ovarian cancer was 45-54 years old (33.6%); the incidence of&#x0D; ovarian cancer decreased with the increased number of parity; the&#x0D; majority histotype was epithelial (76.5%); and most of them were&#x0D; diagnosed on advanced stage (55.1%). The 4-year survival rate for&#x0D; epithelial type was 77%; germinal type was 83.3%; and stromal type&#x0D; was 100%. Based on therapy, the 4-year survival rate was 84.1% for&#x0D; surgical only; 83.3% in adjuvant chemotherapy group; and 68.4% in&#x0D; neoadjuvant chemotherapy. In the group of adjuvant chemotherapy,&#x0D; there was 63% patients with complete response and 41.2% patients&#x0D; with complete response in neoadjuvant chemotherapy.&#x0D; Conclusion: The highest incidence of ovarian cancer in Dr. Cipto&#x0D; Mangunkusumo Hospital belongs to the age of reproductive women&#x0D; (≤ 55 years old) with the highest incidence occurs in nulliparity women.&#x0D; Most of the ovarian cancer cases are diagnosed in advanced&#x0D; stage (stage III-IV).&#x0D; [Indones J Obstet Gynecol 2016; 4-2: 101-106]&#x0D; Keywords: age, histotype, ovarian cancer, parity, response, stage,&#x0D; survival, treatment

Survival Impact of Adjuvant Chemotherapy for Resected Locally Advanced Rectal Adenocarcinoma

BackgroundRecent data has created uncertainty regarding the benefit of adjuvant fluoropyrimidine-containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer (LARC). In particular, patients with a pathologic complete response (pCR) may derive no benefit from adjuvant chemotherapy. Patients and MethodsThis is a retrospective analysis of patients with LARC, diagnosed between January 1, 2003 and December 31, 2014 at 3 Melbourne health services. Patients were identified from the Australian Comprehensive Cancer Outcomes and Research Database, where a defined data set is prospectively collected on consecutive patients. Patient demographics, pCR rates, postoperative treatment, recurrence, and survival were analyzed. ResultsA total of 717 patients with LARC were identified, of whom 555 (77%) had received preoperative long-course chemoradiation followed by surgery. Four hundred fifty-two of 555 patients (81%) subsequently received adjuvant fluoropyrimidine-based chemotherapy. At a median follow-up of 45.9 months, 95 (21%) patients in the adjuvant chemotherapy group and 20 (19%) in the surveillance group had relapsed. Five-year relapse-free survival was 77% in the adjuvant chemotherapy group and 71% in the surveillance group with no significant difference on univariate analysis (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.58-1.51; P = .780). No significant impact on relapse-free survival was seen for either pCR or non-pCR patients. Five-year overall survival (OS) was 85% in the adjuvant chemotherapy group and 74% in the surveillance group with a nonsignificant trend towards OS benefit (HR, 0.62; 95% CI, 0.37-1.05; P = .074). A significant OS benefit favoring adjuvant chemotherapy was seen in the non-pCR subset of patients (HR, 0.49; 95% CI, 0.28-0.86; P = .014). ConclusionA high proportion of patients in this routine practice cohort received adjuvant chemotherapy following preoperative treatment and surgery for LARC. Adjuvant chemotherapy administration was associated with a significant improvement in 5-year OS only in the patients with a non-pCR.

Survival Outcomes for Combined Modality Therapy for Sinonasal Undifferentiated Carcinoma.

Objective Sinonasal undifferentiated carcinoma is a rare and aggressive malignancy of the nasal cavity and paranasal sinuses. Multi-institutional studies examining outcomes of combined modality treatment versus other treatment modalities have not been performed. The objective of our study was to present outcomes for multimodality therapy through use of the National Cancer Database. Study Design Retrospective cohort study. Setting National Cancer Database. Methods A total of 435 cases of SNUC diagnosed between 2004 and 2012 were identified. Kaplan-Meier analyses were performed to find 5-year cumulative survival rates. Multivariate Cox regression evaluated overall survival based on treatment when adjusting for other prognostic factors (age, primary site, sex, race, comorbidity, insurance, and TNM stage). Within the surgery + chemoradiotherapy group, survival analysis was also performed to compare outcomes for induction and adjuvant chemotherapy. Results The cumulative 5-year survival rate was 41.5%, and 36.1% of patients received surgery with chemoradiotherapy. In multivariate analysis, surgery + chemoradiotherapy was associated with significantly improved overall survival versus surgery + radiotherapy and radiotherapy but not significantly different from chemoradiotherapy. Within the surgery + chemoradiotherapy group, induction and adjuvant chemotherapy groups did not have associated differences in survival. Conclusion Combined modality therapy (chemoradiotherapy or surgery + chemoradiotherapy) is associated with improved survival outcomes versus other treatment modalities in patients with sinonasal undifferentiated carcinoma.

Factors influencing receipt of adjuvant chemotherapy after surgery for pancreatic cancer: a two-center retrospective cohort study

Objective: The addition of adjuvant chemotherapy after surgical resection has improved survival rates for patients with pancreatic ductal adenocarcinoma (PDAC). However, outside clinical trials, many operated patients still do not receive adjuvant chemotherapy due to clinical and tumor-related factors. The aim of this study was to investigate factors that may influence the receipt of adjuvant chemotherapy and the effect on long-term survival.Materials and methods: Patients undergoing macroscopically curative resection for PDAC at the University Hospitals in Lund and Linköping, Sweden, between 1 January 2007 and 31 December 2015, were retrospectively reviewed. Clinical and pathological data were compared between adjuvant and non-adjuvant chemotherapy groups and factors affecting chemotherapy receipt were analyzed by multiple logistic regression. Multivariable Cox regression analysis was performed to select predictive variables for survival.Results: A total of 233 patients were analyzed. Adjuvant chemotherapy was administered to 167 patients (71.7%). The likelihood of receiving adjuvant chemotherapy decreased with age, OR 0.91, 95% CI 0.86–0.95, p < .001. Moreover, patients with severe postoperative complications (Clavien–Dindo grade ≥ III) were less likely to receive adjuvant chemotherapy, OR 0.31, 95% CI 0.14–0.71, p = .005. The presence of lymph node metastases on histopathological reporting was associated with increased likelihood of initiating adjuvant chemotherapy, OR 2.19, 95% CI 1.09–4.40, p = .028. Adjuvant chemotherapy was an independent factor for prolonged survival on multivariable Cox regression analysis, HR 0.45 (95% CI 0.31–0.65), p < .001.Conclusions: Age, postoperative complications and the presence of lymph node metastases affect the likelihood of receiving adjuvant chemotherapy after PDAC surgery.

Management of “borderline resectable” and “locally advanced” pancreatic cancer at the Massachusetts General Hospital

Recent data has created uncertainty regarding the benefit of adjuvant fluoropyrimidine-containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer (LARC). In particular, patients with a pathologic complete response (pCR) may derive no benefit from adjuvant chemotherapy.This is a retrospective analysis of patients with LARC, diagnosed between January 1, 2003 and December 31, 2014 at 3 Melbourne health services. Patients were identified from the Australian Comprehensive Cancer Outcomes and Research Database, where a defined data set is prospectively collected on consecutive patients. Patient demographics, pCR rates, postoperative treatment, recurrence, and survival were analyzed.A total of 717 patients with LARC were identified, of whom 555 (77%) had received preoperative long-course chemoradiation followed by surgery. Four hundred fifty-two of 555 patients (81%) subsequently received adjuvant fluoropyrimidine-based chemotherapy. At a median follow-up of 45.9 months, 95 (21%) patients in the adjuvant chemotherapy group and 20 (19%) in the surveillance group had relapsed. Five-year relapse-free survival was 77% in the adjuvant chemotherapy group and 71% in the surveillance group with no significant difference on univariate analysis (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.58-1.51; P = .780). No significant impact on relapse-free survival was seen for either pCR or non-pCR patients. Five-year overall survival (OS) was 85% in the adjuvant chemotherapy group and 74% in the surveillance group with a nonsignificant trend towards OS benefit (HR, 0.62; 95% CI, 0.37-1.05; P = .074). A significant OS benefit favoring adjuvant chemotherapy was seen in the non-pCR subset of patients (HR, 0.49; 95% CI, 0.28-0.86; P = .014).A high proportion of patients in this routine practice cohort received adjuvant chemotherapy following preoperative treatment and surgery for LARC. Adjuvant chemotherapy administration was associated with a significant improvement in 5-year OS only in the patients with a non-pCR.

Evaluation of Clinical Results and Complications of Structural Allograft Reconstruction after Bone Tumor Surgery.

Massive bone allograft is an option in cases of limb preservation and reconstruction after massive benign and malignant bone tumor resection. The purpose of this study was to analyze the outcome of these procedures at Imam Reza Hospital, Mashhad University of Medical Sciences. In this study, 113 cases have been presented. Eleven cases were excluded (patients has a traumatic defect or they passed away before the completion of the study's two-year follow up period). Each patient completed a questionnaire, went through a physical examination and, if indicated, X-ray information was collected. The patients were divided into three groups: chemotherapy, chemotherapy plus radiation therapy, and no-adjuvant-therapy. Fifty-four cases were male and the mean age was 24.5±5.39. The number of cases and indications for surgery were: 33 cases of aggressive benign tumors or low grade malignant bone tumors (large bone defects) including 16 germ cell tumors, eight aneurysmal bone cysts, five low grade osteosarcomas, and four chondrosarcomas. Another 69 cases were high-grade malignant bone tumors including 42 osteosarcomas, 21 Ewing's sarcoma, and six other high grade osteosarcomas. Patients were divided into three groups: the first group received no adjuvant therapy, the second group received chemotherapy, and the third group received chemotherapy plus radiotherapy. The location of tumors were as follows: eight cases in the pelvic bone, 12 in the proximal femur, 18 in the femoral shaft, 36 in the distal femur, 12 in the proximal tibia, and 16 in the humeral bone. The 12 cases of proximal femoral defects were reconstructed by allograft composite prosthesis, 18 diaphyseal defects with intercalary allograft, and 36 distal femoral defects were reconstructed using osteoarticular allograft. The rate of deep infection was 7:8% (eight patients) and in this regard, we found a significant difference among the three groups, such that most cases of infection occurred in the adjuvant chemotherapy plus radiation therapy group. Allograft fracture occurred in six patients and prevalence was the same in all groups. Only in six cases of radio-chemotherapy nonunion occurred, so we used autogenous bone graft for union. Local recurrence was observed in six patients: three belonged to the adjuvant chemotherapy group and the other three were in the chemo-radiotherapy group; no significant difference was observed between these two groups. However, there was a significant difference between these two and the group that received no adjuvant therapy. Also, there were 11 cases of metastases and Restriction of knee joint motion occurred in 48 cases of osteo-cartilaginous grafts of the distal femur and proximal tibia. Although structural allograft is an appropriate choice in limb reconstruction after massive resection of involved tissues in malignant and invasive bone tumors, the risk of complications such as nonunion and infection in massive allograft increases in cases of adjuvant (chemotherapy and radiotherapy) modalities of treatment. Whereas the rate of tumor recurrence, metastasis, and restrictions in range of motion during a short term follow up after implantation showed no significant difference among the evaluated groups. Consequently, further attention and constant periodic visits of the patients and checking for local recurrence and distant metastasis should be done after surgery.

A double-blind and randomized controlled clinical trial of traditional Chinese medicine combined with adjuvant chemotherapy for early stage non-small cell lung cancer

Objective To evaluate the efficacy of adjuvant chemotherapy combined with traditional Chinese medicine (TCM) on the prevention of the radical resected non-small cell lung cancer (NSCLC) relapse and metastasis. Methods A double-blind and randomized controlled clinical trial including 100 patients with radical resected NSCLC enrolled was designed. The subjects were randomly divided into two groups, adjuvant chemotherapy group combine with placebo (control group) and adjuvant chemotherapy combined with TCM group (trial group). 4 cycles of adjuvant chemotherapy [NC regimen: vinorelbine 25 mg/m2, d1 and d8 combined with carboplatin AUC = 5 mg/(ml·min), d1] were used after surgery. The curve of disease free survival (DFS) was drew by Kaplan-Meier test. Two groups' curative effects were compared by repeated measurement of quality of life (QOL) score and TCM symptom score before, during and after treatment. Results The median DFS of trail group was longer than that of control group (36.00 months vs 23.98 months, P = 0.047). Stratification analysis showed that DFS of trial group was longer than that of control group for the Ⅰ-Ⅱ stage patients (35.32 months vs 28.82 months, P = 0.037), and DFSs of both groups for patients in ⅢA stage were no difference (P = 0.555). TCM symptom complex score of the trail group was decreased after treatment and had a significantly statistical difference (P = 0.022). Cox multivariate analysis showed that the tumor stage was the main influence factor of DFS (P = 0.000). Physical function, role function, emotional function, and overall health status were significantly improved after treatment (P < 0.05). In the related symptoms, fatigue, pain, insomnia were gradually improved with the extension of treatment time and the implementation of the supplementary treatment, but there was no significant difference in the QOL between the two groups. In the trail group, there were 8 cases of adverse events, which was less than that in the control group (14 cases) (P = 0.045). Conclusion Adjuvant chemotherapy combined with TCM can prolong the DFS of patients with radical resected NSCLC, reduce recurrence rate, relieve the adverse effects of chemotherapy, and improve the clinical and Chinese medical symptoms. Key words: Carcinoma, non-small-cell lung; Postoperative adjuvant chemotherapy; Adjuvant chemotherapy combined with traditional Chinese medicine; Disease-free survival; Quality of life; Chinese medicine symptom

Adjuvant gemcitabine monotherapy for resectable perihilar cholangiocarcinoma with lymph node involvement: a propensity score matching analysis.

The aim of this study was to evaluate the efficacy of adjuvant gemcitabine monotherapy following resection for perihilar cholangiocarcinoma with lymph node involvement. We performed a retrospective analysis of 180 patients undergoing resection for perihilar cholangiocarcinoma with lymph node involvement between 2001 and 2012. The patients were divided into two groups according to the presence (n=67) or absence (n=113) of adjuvant gemcitabine monotherapy. Univariate and multivariate analyses were performed followed by a propensity score matching analysis to adjust for the differences in the baseline characteristics of the groups. The overall survival rates after surgery and the median survival times in patients who were treated with adjuvant chemotherapy were significantly longer than those who were treated without adjuvant chemotherapy (32.9 vs. 15.0% at 5years, 37 vs. 20months, P=0.001). A multivariate analysis indicated that adjuvant chemotherapy, a residual microscopic tumor, and pathological T stage were independent prognostic factors for survival. After two new cohorts of 32 patients were generated following 1:1 propensity score matching, the overall survival rate in the adjuvant chemotherapy group was found to be significantly longer than that in the surgery alone group (43.2 vs. 15.6% at 5years, P=0.001). Adjuvant gemcitabine monotherapy may improve survival in node-positive perihilar cholangiocarcinoma patients.

Significance of the Complete Surgical Staging of Stage I Malignant Ovarian Germ Cell Tumors.

The aim of this study was to evaluate the role of complete surgical staging of a malignant ovarian germ cell tumor (MOGCT) that is apparently confined to the ovaries. This retrospective study included 135 patients with stage I MOGCT after surgery. Patients who were categorized with stage I disease without complete staging operation were staged as IX. Statistical analysis was performed using Chi-squared or Fisher's exact tests and a Cox proportional hazards model. Eighty-six patients (62.7%) underwent a complete staging operation; 43 had stage IA disease, 3 had stage IB disease, and 40 had stage IC disease. Forty-nine patients (36.3%) were staged as IX. After surgery, 93 patients (68.8%) received adjuvant chemotherapy. In the observation group, the recurrence rates were 12.5% (2/16), 14.3% (1/7), and 47.4% (9/19) for stage IA-IB, stage IC, and stage IX disease, respectively (stage IA-IB vs. stage IX, p=0.035; stage IC vs. stage IX, p=0.190). In the adjuvant chemotherapy group, the recurrence rates were 6.7% (2/30), 6.1% (2/33), and 6.7% (2/30) for stage IA-IC, stage IC, and stage IX disease, respectively (stage IA-IC vs. stage IX, p>0.999; stage IC vs. stage IX, p>0.999). In multivariable survival analysis, complete surgical staging was significantly associated with improved disease-free survival in patients with stage I MOGCT (odds ratio 3.2; 95% confidence interval 1.1-9.9; p=0.049). Complete surgical staging is independently associated with prognosis in women with apparently early MOGCT who did not receive adjuvant chemotherapy. To enter surveillance strategy without adjuvant chemotherapy, complete surgical staging is mandatory.