[Role of neoadjuvant rectal score in prognosis and adjuvant chemotherapy decision-making in locally advanced rectal cancer following neoadjuvant short-course radiotherapy and consolidation chemotherapy].

Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

[Stereotactic body radiation therapy for patients with lung and liver oligometastases from colorectal cancer: a phase â ¡ trial].

Objective: To explore the safety and effectiveness of stereotactic body radiation therapy (SBRT) for oligometastases from colorectal cancer (CRC). Methods: This is a prospective, single-arm phase Ⅱ trial. Patients who had histologically proven CRC, 1 to 5 detectable liver or lung metastatic lesions with maximum diameter of any metastases ≤5 cm were eligible. SBRT was delivered to all lesions. The primary endpoint was 3-year local control (LC). The secondary endpoints were treatment-related acute toxicities of grade 3 and above, 1-year and 3-year overall survival (OS) and progression free survival (PFS). Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: Petients from 2016 to 2019 who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Forty-eight patients with 60 lesions were enrolled, including 37 liver lesions and 23 lung lesions. Forty-six patients had 1 or 2 lesions, with median diameter of 1.3 cm, the median biologically effective dose (BED(10)) was 100.0 Gy. The median follow-up was 19.5 months for all lesions. Twenty-five lesions developed local failure, the median local progression free survival was 15 months. The 1-year LC, OS and PFS was 70.2% (95% CI, 63.7%~76.7%), 89.0% (95% CI, 84.3%~93.7%) and 40.4% (95%CI, 33.0%~47.8%). The univariate analysis revealed that planning target volume (PTV) and total dose were independent prognostic factors of LC (P<0.05). For liver and lung lesions, the 1-year LC, OS and PFS was 58.7% and 89.4% (P=0.015), 89.3% and 86.5% (P=0.732), 30.5% and 65.6% (P=0.024), respectively. No patients developed acute toxicity of grade 3 and above. Conclusion: SBRT is safe and effective treatment method for oligometastases from CRC under precise respiratory motion management and robust quality assurance.

[Treatment and prognostic analysis of isolated chest wall recurrence of breast cancer after mastectomy].

Objective: To analyze the prognostic factors of breast cancer patients with isolated chest wall recurrence (ICWR) after mastectomy, and investigate the optimal treatment. Methods: A total of 201 breast cancer patients with ICWR after mastectomy who were treated in Cancer Hospital, Chinese Academy of Medical Sciences and the Fifth Medical Center Chinese PLA General Hospital from October 1998 to April 2018 were retrospectively analyzed. The median follow-up was 92.8 months and survival data were obtained. Results: Among 201 patients with ICWR, 103 patients developed subsequent locoregional recurrence (sLRR) and 5-year cumulative sLRR rate was 49.1%; 134 patients developed distant metastasis (DM) and 5-year DM rate was 64.4%; 103 patients died, the median progression-free survival (PFS) was 17.4 months and the 5-year PFS rate was 23.2%; the median overall survival (OS) was 62.5 months and the 5-year OS rate was 52.1%. Multivariate analysis showed that the recurrence interval (HR=2.17, 95% CI: 1.26-3.73) and the locoregional treatment (HR=1.59, 95% CI: 1.05-2.40) were the independent prognostic factors for sLRR. The initial HER2 status (HR=1.60, 95% CI: 1.03-2.48) was the independent prognostic factor for DM. The recurrence interval (HR=1.99, 95% CI: 1.30-3.04), the locoregional treatment (HR=1.99, 95% CI: 1.43-2.76) and the treatment modalities after recurrence (HR=1.70, 95% CI: 1.18-2.46) were the independent prognostic factors for PFS. The initial HER2 status (HR=1.69, 95% CI: 1.02-2.81), the recurrence interval (HR=1.85, 95% CI: 1.15-2.98) and the treatment modalities after recurrence (HR=2.48, 95% CI: 1.56-3.96) were the independent prognostic factors for OS. Conclusions: Breast cancer patients after ICWR have an optimistic OS until now, but the risk of sLRR and DM is high. Comprehensive treatment modalities including surgery, radiotherapy and systemic therapy improve the outcome of breast cancer patients with ICWR after mastectomy.

[Comparison of preoperative chemotherapy with concurrent chemoradiotherapy combined with TME for 305 patients with locally advanced rectal cancer].

Objective: To retrospectively analyze the long-term efficacy and prognostic factors of preoperative chemotherapy (PCT) or chemoradiotherapy (PCRT) combined with total mesorectal excision in locally advanced rectal cancer. Methods: Clinical pathology data of 305 patients with localized advanced rectal cancer admitted to the Cancer Hospital, Chinese Academy of Medical Sciences from 2006 to 2018 were collected, of whom 246 patients received PCRT (PCRT group), 59 patients received PCT (PCT group). Kaplan-Meier and Log rank test were used for the survival analysis, Cox regression model was used for multivariate analysis, and the prognosis of two groups of patients were compared by the propensity score matching (PSM). Results: In the whole group of 305 patients, 20 cases of tumors located in the upper part of the rectum and at the junction of rectum and colon, 96 cases in the middle of the rectum and 189 cases in the lower part of the rectum. PCRT group included 38 cases of cT2-3 phase, 11 cases of cT4a stage, 10 cases of cT4b stage, while the cases in PCT group were 184, 0 and 62 cases, respectively, the difference is statistically significant (P<0.05). The R0 excision rates of PCRT group and PCT group were 100% (246/246) and 96.6% (57/59), respectively, and the total pathological remission rates were 13.4% and 3.3%, respectively (P<0.05). After PSM, the 3-year survival rates of PCRT group and the PCT group were 86.6% and 89.9% (P>0.05), respectively, and the progression-free survival rates were 74.6% and 77.2% (P>0.05), local recurring free survival rates were 100% and 92.3% (P>0.05), distant metastasis free survival rate were 75.6% and 77.3% (P>0.05). Pre-treatment N-positive, N-degeneration and MRF-positive were all associated with total survival (P<0.05). Conclusion: In the PCRT group, with a higher proportion of patients with stage T4b and lower rectal cancer, the long-term efficacy of PCRT was similar to that of PCT, and higher R0 excision rate and pathological complete response rate could be obtained.

The function of floral traits and phenotypic selection in Aconitum gymnandrum (Ranunculaceae).

Floral evolution in angiosperms is thought to be driven by pollinator-mediated selection. Understanding flower integration and adaptation requires resolving the additive and nonadditive contributions of floral pollinator attraction and pollination efficiency traits to fitness components. In this study, a flower manipulation experiment with a factorial design was used to study the adaptive significance of galea height (a putative attraction trait) and entrance width (a putative efficiency trait) in Aconitum gymnandrum Maxim. flowers. Simultaneously, phenotypic selection analysis was conducted to examine selection by pollinators on galea height, entrance width, nectar production and plant height. Increased galea height increased the pollinator visitation rate, which confirmed its attractiveness function. Increasing floral entrance width by spreading the lower sepals increased the seed number per fruit without affecting pollinator visitation. This suggests a pollination efficiency role for the entrance width. The phenotypic selection analysis, however, did not provide evidence of pollinator-mediated selection for either of these traist, but it did for plant height. According to the manipulation treatment and correlational selection results, the combined variation in galea height and entrance width of A. gymnandrum flowers did not have nonadditive effects on female reproductive success. This study demonstrated the adaptive value of A. gymnandrum flowers through manipulation of an attractiveness trait and an efficiency trait. However, neither trait was associated with pollinator-mediated selection. A combination of manipulating traits and determining current phenotypic selection could help to elucidate the mechanism of selection on floral traits involved in different functions and flower integration.

[A nomogram to predict non-sentinel lymph node metastasis for breast cancer patients with positive axillary sentinel lymph node].

Objective: To identify the risk factors of non-sentinel lymph node (nSLN) metastasis in breast cancer patients with 1~2 positive axillary sentinel lymph node (SLN) and construct an accurate prediction model. Methods: Retrospective chart review was performed in 917 breast cancer patients who underwent surgery treatment between 2002 and 2017 and pathologically confirmed 1-2 positive SLNs. According to the date of surgery, patients were divided into training group (497 cases) and validation group (420 cases). A nomogram was built to predict nSLN metastasis and the accuracy of the model was validated. Results: Among the 917 patients, 251 (27.4%) had nSLN metastasis. Univariate analysis showed tumor grade, lymphovascular invasion (LVI), extra-capsular extension (ECE), the number of positive and negative SLN and macro-metastasis of SLN were associated with nSLN metastasis (all P<0.05). Multivariate Logistic regression analysis showed the numbers of positive SLN, negative SLN and macro-metastasis of SLN were independent predictors of nSLN metastasis (all P<0.05). A nomogram was constructed based on the 6 factors. The area under the receiver operating characteristic curve was 0.718 for the training group and 0.742 for the validation group. Conclusion: We have developed a nomogram that uses 6 risk factors commonly available to accurately estimate the likelihood of nSLN metastasis for individual patient, which might be helpful for radiation oncologists to make a decision on regional nodal irradiation.

[Subclinical heart injury in patients receiving hypofractionated radiotherapy after breast conserving surgery: a preliminary analysis of prospective study].

Objective: To evaluate the incidence of early cardiac injury in patients with left-sided breast cancer receiving hypofractionated radiotherapy after breast conserving surgery, and to investigate the correlation between cardiac injury and hypofractionated radiotherapy dose. Methods: We prospectively enrolled 103 breast cancer patients who received whole breast with or without regional nodal irradiation after breast conserving surgery using either deep inspiration breath-hold (DIBH) or free breathing (FB) radiotherapy technique. Cardiac examinations that included N-terminal pro-B-type natriuretic peptide (NT-proBNP), electrocardiogram, and myocardial perfusion imaging were performed routinely before and after radiotherapy. The effects of heart dose, systemic therapy and individual factors (Framingham score) on the incidence of cardiac events were analyzed. Results: The median age was 48 years. The mean dose (Dmean) of the heart, left anterior descending coronary artery (LAD), left ventricular (LV), and right ventricular (RV) were 4.0, 16.9, 6.3, and 4.4 Gy, respectively. With a median follow-up of 13.4 months, no patient had clinical cardiac abnormalities. The incidence rates of subclinical cardiac events at 1- 6- and 12-month were 23.5%, 31.6%, and 41.3%, respectively. The DIBH group had a lower mean dose, maximum dose, and V5-V40 in the heart, LAD, LV, and RV than the FB group (P<0.001). Univariate analysis showed an increased incidence of subclinical cardiac events with heart Dmean >4 Gy, LAD V40 > 20%, LV Dmean >6 Gy, RV Dmean >7 Gy, or cumulative doses of anthracycline or taxane > 300 mg/m(2) (All P<0.05). Anti-HER2 targeted therapy, endocrine therapy and Framingham score were not associated with the incidence of subclinical cardiac events (all P>0.05). Multivariate analysis demonstrated that Dmean of LV and RV were independently associated with the increased incidence of subclinical cardiac events. Conclusions: Early subclinical heart injury are found in patients with left-sided breast cancer after hypofractionated radiotherapy. The increased incidence of subclinical cardiac events after radiotherapy is positively associated with the cardiac radiation doses.

[The 8th edition of the American Joint Committee on Cancer staging system provide improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients].

Objective: To validate whether the prognostic stage groups by the 8th edition of the American Joint Committee on Cancer (AJCC) staging system provides improved prognostic accuracy in T1-2N1M0 postmastectomy breast cancer patients compared to 7th edition. Methods: a total of 1 823 female patients with T1-2N1M0 breast cancer who underwent mastectomy and axillary lymph node dissection without neoadjuvant chemotherapy were analyzed and restaged according to 8th edition. Univariate analysis of prognostic factors was evaluated by using log-rank test. Multivariate analysis was estimated by using the Cox proportional hazards model. The prognostic accuracy of the two staging systems was compared using receiver operating characteristic (ROC) analyses and the concordance index (C-index). Results: 5-year locoregional recurrence rate (LRR) for the whole group was 6.0%, 5-year distant metastasis (DM) rate was 11.5%, 5-year disease-free survival (DFS) was 85.0%, and 5-year overall survival (OS) was 93.1%. Cox analysis showed that 7th edition of the AJCC staging system and progesterone receptor status were independent risk factors for LRR, DM, DFS and OS (P<0.05). Compared with stage by 7th edition, 1 278(70.1%) were assigned to a different prognostic stage group: 1 088 (85.1%) to a lower stage and 190 (14.9%) to a higher stage. LRR, DM, DFS and OS were significantly different between prognostic stage ⅠA, ⅠB, ⅡA, ⅡB and ⅢA according to 8th edition of the AJCC staging system(P<0.001). Prognostic stage had significantly higher C-indexes and provided better estimation of prognosis compared to stage by 7th edition of the AJCC staging system (P<0.001). Conclusion: The prognostic stage groups of 8th edition AJCC staging system has superior prognostic accuracy compared to 7th edition in T1-2N1M0 breast cancer, and has better clinical therapeutic guidance value.

[Clinical differences between primary nasopharyngeal NK/T-cell lymphoma and primary nasal cavity NK/T-cell lymphoma with nasopharynx extension].

Objective: To investigate the clinical and prognostic differences between primary nasopharyngeal natural killer (NK)/T-cell lymphoma (NP NKTCL) and extranodal NK/T-cell lymphoma of the nasal cavity with nasopharynx extension (N-NP NKTCL). Methods: A total of 89 patients with NP NKTCL and 113 patients with N-NP NKTCL from January 2000 to June 2015 were retrospectively analyzed. Clinical and pathological features, treatment responses and prognosis were compared between the two groups. Results: NP NKTCL patients showed similar clinicopathological features with those with N-NP NKTCL, except that the former had a relative low proportion of elevated lactate dehydrogenase (LDH) levels (28.1% vs. 41.6%; P=0.001). Both of two groups presented with high proportion of cervical lymph node involvement (55.1% and 42.5%; P=0.076). The 5-year overall survival (OS) rates in these two groups were 63.2% and 54.6%, respectively, whereas 5-year progress-free survival (PFS) rates were 50.7% and 45.6%, respectively. For the patients with stage Ⅰ and Ⅱ, the 5-year OS and PFS rates in these two groups were 68.8% and 55.7% as well as 55.6% and 47.2%, respectively. These were no statistically significant differences between two groups (all P>0.05). The complete response (CR) rate after initial chemotherapy in NP NKTCL group was 43.8%, which was significant higher than that of 19.6% in N-NP NKTCL group (P=0.006). Additionally, the CR rate after primary radiotherapy was 63.4% and 62.7%, respectively (P=0.629). The NP NKTCL patients with stage Ⅰ and Ⅱ who accepted radiotherapy with or without chemotherapy had similar survival times with chemotherapy alone, showing the 5-year OS rates of 70.5% and 33.3% (P=0.238), as well as the 5-year PFS rates of 56.7% and 33.3%, respectively (P=0.431). Similar results were found in N-NP NKTCL group, the 5-year OS rates for patients with radiotherapy with or without chemotherapy and chemotherapy alone were 57.4% and 33.3% (P=0.246), while the 5-year PFS rates were 49.3% and 16.7% (P=0.177), respectively. Besides, the relapse pattern of NP NKTCL and N-NP NKTCL groups was also similar, mainly involving the distant extra-nodal organs followed by lymph nodes. Conclusion: The patients with N-NP NKTCL and NP NKTCL showed similar clinical and prognostic features, however, the initial response to chemotherapy was different.

[Risk-adapted postmastectomy radiotherapy based on local-regional recurrence for T1-2N1M0 breast Cancer].

Objective: To establish a risk-adapted postmastectomy radiotherapy strategy based on local-regional recurrence for intermediate-risk breast cancer (T1~2N1M0 stage). Methods: A total of 2413 patients with T1-2N1M0 breast cancer were retrospectively reviewed. Of them, 588 patients (24.4%) received postmastectomy radiotherapy (PMRT), while 1 825 (75.6%) patients did not. A comprehensive comparative study was performed by using multivariable and propensity score-matched (PSM) analyses. Results: The median follow-up time was 67.0 months, the 5-year local region recurrence free-survival (LRRFS), disease-free survival (DFS) and overall survival (OS) were 93.8%, 85.7% and 93.3%, respectively. The 5-year local region recurrence (LRR) was 6.1%. For patients without PMRT, multivariable analysis indicated that age, tumor localization, molecular subtype, pathologic T stage and number of positive lymph node were independent factors for LRRFS (all of P<0.05). Patients with T1-2N1 breast cancer were classified into low-risk group (0-1 risk factor, 768 patients), intermediate-risk group (2 risk factors, 690 patients) and high-risk groups (≥3 risk factors, 544 patients) based on the five independent factors mentioned above. The 5-year LRRFS, DFS and OS were significantly different among the three groups (P<0.001). In low- and intermediate-risk groups, there were no significant differences in LRRFS, DFS and OS of patients who received PMRT or not (P>0.05). In high-risk group, the DFS of patients received PMRT or not were 79.8% and 74.4%, respectively (P=0.127), the OS of them were 86.8% and 87.1%, respectively (P=0.174), and the LRRFS were 93.3% and 84.3%, respectively (P=0.002). After PSM adjustment, no significant differences in LRRFS, DFS and OS were observed between PMRT-received subgroup and no PMRT subgroup of low-risk group (P>0.05). In intermediate-risk group, the LRRFS of patients received PMRT or not were 95.2% and 91.0%, respectively (P=0.037). However, in the high-risk group, the LRRFS, DFS and OS of patients received PMRT were 93.3%, 79.7% and 86.6%, respectively, while those of patients did not receive PMRT were 78.5% (P<0.001), 69.5% (P=0.038) and 85.7% (P=0.080), respectively. Conclusions: The local-regional recurrence risks of patients with pT1-2N1 breast cancer are viable and risk-adapted PMRT is available for them. Better prognoses can be achieved by the patients of intermediate and high-risk group. More samples on this subject are needed to validate the results.

[Prognostic differences of phenotypes in pT1-2N0 invasive breast cancer: a large cohort study with cluster analysis].

OBJECTIVE: To find phenotypic subgroups of patients with pT1-2N0 invasive breast cancer by means of cluster analysis and estimate the prognosis and clinicopathological features of these subgroups. METHODS: From 1999 to 2013, 4979 patients with pT1-2N0 invasive breast cancer were recruited for hierarchical clustering analysis. Age (≤40, 41-70, 70+ years), size of primary tumor, pathological type, grade of differentiation, microvascular invasion, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) were chosen as distance metric between patients. Hierarchical cluster analysis was performed using Ward's method. Cophenetic correlation coefficient (CPCC) and Spearman correlation coefficient were used to validate clustering structures. RESULTS: The CPCC was 0.603. The Spearman correlation coefficient was 0.617 (P<0.001), which indicated a good fit of hierarchy to the data. A twelve-cluster model seemed to best illustrate our patient cohort. Patients in cluster 5, 9 and 12 had best prognosis and were characterized by age >40 years, smaller primary tumor, lower histologic grade, positive ER and PR status, and mainly negative HER-2. Patients in the cluster 1 and 11 had the worst prognosis, The cluster 1 was characterized by a larger tumor, higher grade and negative ER and PR status, while the cluster 11 was characterized by positive microvascular invasion. Patients in other 7 clusters had a moderate prognosis, and patients in each cluster had distinctive clinicopathological features and recurrent patterns. CONCLUSIONS: This study identified distinctive clinicopathologic phenotypes in a large cohort of patients with pT1-2N0 breast cancer through hierarchical clustering and revealed different prognosis. This integrative model may help physicians to make more personalized decisions regarding adjuvant therapy.

Transcatheter arterial chemoembolization combined with radiofrequency ablation can improve survival of patients with hepatocellular carcinoma with portal vein tumour thrombosis: extending the indication for ablation?

AIM: To retrospectively assess long-term survival benefit and safety of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) in hepatocellular carcinoma (HCC) patients with portal vein tumour thrombosis (PVTT), and to evaluate factors that significantly affect outcomes of these patients. MATERIALS AND METHODS: One hundred and thirty-four HCC patients (118 men and 16 women; mean age 54.8 years, range 26-79 years) with PVTT were retrospectively assessed. Patients were treated with TACE combined with RFA. Data analysed included patient demographics, liver volume, Child-Pugh score, and Cancer of the Liver Italian Programme (CLIP) score and imaging findings. Survival time (from occurrence of PVTT to last follow-up) was calculated using the Kaplan-Meier method, predictive factors and its correlation with survival was assessed using the multivariate Cox proportional hazards regression method. RESULTS: The median overall survival (OS) time was 29.5 months (range 16.6-42.4 months), the 1, 3, and 5 year OS were 63%, 40%, and 23%. Cox hazards regression analysis revealed that functional remnant liver volume (FRLV), remnant liver volume (RLV)/total liver volume (TLV), radiation, tumour number, vascular endothelial growth factor (VEGF) distribution, and gross type were the only independent predictive factors of outcome (p = 0.039, 0.010, 0.009, 0.034, 0.031, and 0.000, respectively). CONCLUSION: TACE combined with RFA was found to be an effective therapy, FRLV and RLV/TLV have close correlation with survival for HCC patients with PVTT type I, II, or partial III and Child-Pugh A or B.