Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

Aim

To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS).

Materials and methods

Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan–Meier were performed.

Results

Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p < 0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR = 5.6, p < 0.001), positive SN (RR = 5.0, p < 0.001) and male sex (RR = 2.9, p = 0.001). The presence of a metastatic SN (RR = 8.4, p < 0.001), male sex (RR = 6.1, p < 0.001), Breslow thickness (RR = 3.2, p = 0.013) and ulceration (RR = 2.6, p = 0.015) were significantly associated with a poorer DSS.

Conclusion

SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure.     

Cross-validation analysis of the prognostic significance of mucin expression in patients with resected non-small cell lung cancer treated with adjuvant chemotherapy: Results from IALT,JBR.10 and ANITA

Introduction

CALGB 9633 was a randomized trial of observation versus adjuvant chemotherapy for patients with stage IB non-small cell lung cancer (NSCLC). In CALGB 9633, the presence of mucin in the primary tumor was associated with shorter disease-free survival (DFS; hazard ratio (HR) = 1.9, p = 0.002) and overall survival (OS; HR = 1.9, p = 0.004).

Methods

To validate these results, mucin staining was performed on primary tumor specimens from 780 patients treated on IALT, 351 on JBR.10 and 150 on ANITA. The histochemical technique using mucicarmine was performed. The prognostic value of mucin for DFS and OS was tested in a Cox model stratified by trial and adjusted for clinical and pathological factors. A pooled analysis of all 4 trials was performed for the predictive value of mucin for benefit from adjuvant chemotherapy.

Results

The cross-validation group had 48% squamous, 37% adenocarcinoma and 15% other NSCLC compared with 29%, 56%, and 15%, respectively in CALGB. Among 1262 patients with assessable results, mucin was positive in IALT 24%, JBR.10 30%, ANITA 22% compared with 45% in CALGB. Histology was the only significant covariate (p < 0.0001) in multivariate analysis with mucin seen more commonly in adenocarcinoma (56%) compared with squamous (5%) and other NSCLC (15%). Mucin was a borderline negative prognostic factor for DFS (HR = 1.2 [1.0–1.5], p = 0.06) but not significantly so for OS (HR = 1.1 [0.9–1.4], p = 0.25). Prognostic value did not vary according to histology: HR = 1.3 [1.0–1.6] in adenocarcinoma vs. 1.6 [1.2–2.2] for DFS in other histology (interaction p = 0.69). Mucin status was not predictive for benefit from adjuvant chemotherapy (test of interaction: DFS p = 0.27; OS p = 0.49).

Conclusions

Mucin was less frequent in the cross-validation group due to its higher percentage of squamous cell carcinomas. The negative impact of mucin was confirmed for DFS but not for OS. Mucin expression was not predictive of overall survival benefit from adjuvant chemotherapy.     

Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection

Purpose

To evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT).

Methods

Between October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤0.15 [n = 80], 0.16–0.3 [n = 44], >0.3 [n = 30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS).

Results

LNR (≤0.15, 0.16–0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p < 0.001) and DFS (66.7%, 55.8%, and 21.9%; p < 0.001) rates. In a multivariate analysis, LNR (≤0.15, 0.16–0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p < 0.001) and DFS (HRs, 1, 1.699, and 3.960; p < 0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥12 harvested LNs (p < 0.05).

Conclusion

LNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.     

Positive prognostic impact of miR-210 in non-small cell lung cancer

Objectives

miR-210 is an important regulator of the cellular response to hypoxia. Therefore, we aimed to explore the prognostic significance of miR-210 in non-small cell lung cancer (NSCLC) patients with stage I-IIIA disease.

Materials and methods

In addition to clinicopathological and demograpic information, tumor tissues were collected and tissue micro arrays (TMAs) were constructed from 335 patients with stage I-IIIA NSCLC. Expression of miR-210 in cancer cells and stromal cells of the tumor was assessed by in situ hybridization.

Results

In univariate analyses, high cancer cell (p = 0.039) and high stromal cell expression (p = 0.008) of miR-210 were both significantly associated with an improved disease-spesific survival (DSS). High co-expression of miR-210 in cancer and stromal cells was also a positive prognostic factor for DSS (p = 0.010). In multivariate analysis, miR-210 in stromal cells (p = 0.011), and miR-210 co-expressed in cancer and stromal cells was an independent prognosticator for DSS (p = 0.011).

Conclusions

We show that miR-210 in stromal cells, and co-expressed in cancer cells and stromal cells mediates an independent prognostic impact. It is a candidate marker for prognostic stratification in NSCLC.     

The importance of actual tumor growth rate on disease free survival and overall survival in laryngeal squamous cell carcinoma

Background and purpose

Evaluation of the variation in tumor growth rate and the influence of tumor growth rate on disease free survival (DFS) and overall survival (OS) in laryngeal squamous cell carcinoma (LSCC).

Material and methods

We delineated tumor volume on a diagnostic and planning CT scan in 131 patients with laryngeal squamous cell carcinoma and calculated the tumor growth rate. Primary endpoint was DFS. Follow up data were collected retrospectively.

Results

A large variation in tumor growth rate was seen. When dichotomized with a cut-off point of −0.3 ln(cc/day), we found a significant association between high growth rate and worse DFS (p = 0.008) and OS (p = 0.013). After stepwise adjustment for potential confounders (age, differentiation and tumor volume) this significant association persisted. However, after adjustment of N-stage association disappeared. Exploratory analyses suggested a strong association between N-stage and tumor growth rate.

Conclusions

In laryngeal squamous cell carcinoma, there is a large variation in tumor growth rate. This tumor growth rate seems to be an important factor in disease free survival and OS. This tumor growth rate is independent of age, differentiation and tumor volume associated with DFS, but N-stage seems to be a more important risk factor.     

Equivalent survival in patients with advanced stage IB–II and III–IVA cervical cancer treated by adjuvant surgery following chemoradiotherapy

Objectives

To evaluate survival in patients with advanced cervical cancer who underwent surgery after concurrent chemoradiotherapy.

Methods

One hundred and forty-four patients with biopsy-proven stage IB–IVA cervical cancer underwent adjuvant surgery after concurrent chemoradiotherapy. Surgical resection was classified as curative (no evidence of remaining disease after surgery) or palliative (remaining disease after surgery). Endpoints were pelvic control, overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis included tumour FIGO stage, type of surgery (curative versus palliative), pelvic control, response to chemoradiotherapy and lymphatic status.

Results

Tumour FIGO stages were IB–II in 91 cases and III–IVA in 53 cases. Surgery was curative in 127 cases. Pelvic control was achieved in 114 patients and was equivalent in stage IB–II and III–IVA patients. So far, 60 patients have died. The 5-year OS and DFS rates were, respectively, 57.6% [95% CI: 49.1–67.5] and 65% [95% CI: 56.2–75]. OS was significantly affected by the type of surgery (p < 2.10⁻¹⁶), the presence of tumoural residue (p = 0.002) and the pelvic lymphatic status (p < 0.001). DFS was affected by the pelvic (p = 0.02) and para-aortic lymphatic status (p = 0.009). No significant difference was observed between OS and DFS in stage IB–II and III–IVA patients, whereas a macroscopic tumoural residue was observed in, respectively, 30.9 and 52.2% of cases (p = 0.022).

Conclusion

Survival rates were equivalent between patients with IB–II and III–IVA cervical cancer, suggesting that adjuvant surgery following chemoradiotherapy may improve local control.     

The prognostic significance of extracapsular lymph node involvement in node positive patients with colonic cancer

Aims

In colonic cancer the prognostic significance of extracapsular lymph node involvement (LNI) is not established and is therefore the objective of this study.

Methods

Between January 1994 and May 2005, all patients who underwent resection for primary colonic cancer with lymph node metastasis were reviewed. All resected lymph nodes were re-examined to assess extracapsular LNI. In uni- and multivariate analysis disease-free survival (DFS) was correlated with various clinicopathologic factors.

Results

One hundred and eleven patients were included. In 58 patients extracapsular LNI was identified. Univariate analysis revealed that pN-stage (5-year DFS pN1 vs. pN2: 65% vs. 14%, p < 0.001), extracapsular LNI (5-year DFS intracapsular LNI vs. extracapsular LNI: 69% vs. 41%, p = 0.003), and lymph node ratio (5-year DFS <0.176 vs. ≥0.176: 67% vs. 42%, p = 0.023) were significant prognostic indicators. Among these variables pN-stage (hazard ratio 3.5, 95% confidence interval [CI]: 1.72–7.42) and extracapsular LNI (hazard ratio 1.98, 95% CI: 1.00–3.91) were independent prognostic factors. Among patients without extracapsular LNI, those receiving adjuvant chemotherapy had a significantly better survival (p = 0.010). In contrast, chemotherapy did not improve DFS in patients with extracapsular LNI.

Conclusion

Together with pN2 stage, extracapsular LNI reflects a particularly aggressive behaviour and has significant prognostic potential.     

Patterns of lymph node spread and its influence on outcome in resectable parotid cancer

Aim

To assess the metastatic topography of intraparotideal and neck lymph nodes in parotid cancer and its influence on tumour recurrence and survival.

Methods

The lymph node spread of 142 patients with primary parotid carcinoma treated from 1986 to 2006 was analysed. Disease-free survival (DFS) and overall survival (OS) were calculated. The role of the metastatic pattern as prognostic factors were univariately and multivariately analysed.

Results

A lateral, total or radical parotidectomy was performed in 19, 80 and 43 patients, respectively. A radical/radical-modified or selective neck dissection was performed in 68 and 74 patients, respectively. Eighty-seven neck dissection specimens were negative (pN0). Twelve patients had intraparotideal and cervical lymph node involvement (pPar+/pN+). In 24 patients only intraparotideal metastases were detected (pPar+/pN0). 19 patients only had cervical nodal involvement (pPar−/pN+). Twenty-five patients had occult locoregional lymph metastases (cN0/pN+). The median follow-up was 24.4 months. The disease-free survival rate was 81% at 5 years, and 62% at 10 years. By univariate analysis, R+ (p = 0.001), pT (p = 0.019), lymphangiosis carcinomatosa (p = 0.019), pN+ (p = 0.042), and extracapsular spread (p = 0.046) were prognostic for disease-free survival. Multivariate analysis revealed R+ as independent risk factor (p = 0.046). In pN+ patients, involvement of parotid lymph nodes (p = 0.013), nodes in neck level I (p < 0.0001) and IV (p = 0.005) were univariate risk factors. Multivariate analysis showed lymph node metastases in level I as independent risk factor (p = 0.022).

Conclusion

Total parotidectomy and radical-modified neck dissection is recommended as surgical treatment of parotid cancer and should be analysed in a prospective trial.     

Adjuvant extension of chemotherapy after neoadjuvant therapy may not improve outcome in early-stage breast cancer

Introduction

Neoadjuvant chemotherapy (NAC) is equivalent to adjuvant therapy (AdC) in terms of survival and disease-free interval. Many institutions add AdC after NAC and surgery. However, such extended chemotherapy (ExC) is not evidence based. Study aim was to investigate if ExC improved disease-free (DFS) and overall survival (OS).

Patients and Methods

From 1998 to 2006 356 consecutive patients received NAC (45 pts), AdC (221 pts) or ExC (90 pts). We analysed these 3 groups to determine effects of ExC and to identify patients who might benefit. NAC consisted in 93% of 3–6 cycles of epirubicin + docetaxel, AdC comprised EC ± taxanes in 72%. Median age in the NAC, AdC, and ExC-groups was 54, 56 and 52 years with follow-up of 30, 57, and 55 months.

Results

After NAC, 35% achieved downstaging and 10% pathologic complete remission. Surprisingly ExC seemed to result in reduction of 5-year DFS: compared to 85% and 82% after NAC and AdC, DFS was 61% after ExC (p = 0.001). OS was not significantly affected (79, 91, and 78% after NAC, AdC and ExC, p = 0.13). In multivariate analysis after correction for age, menopausal status, stage, grading, hormone receptors, her2-status, radiotherapy and surgery, ExC seemed to adversely affect DFS (HR 2.15, p = 0.008), loco-regional and distant recurrence-rates (HR 3.0, p = 0.03 and HR 2.0, p = 0.02).

Discussion

In this single-center analysis ExC could not show advantages in terms of DFS and OS. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials. Until then, extended chemotherapy should be considered carefully. As in previous studies, no differences were found between NAC and AdC groups.     

Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trial

Background and purpose

To report the long-term results of a single-institution randomized study comparing the results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI).

Patients and methods

Between 1998 and 2004, 258 selected women with pT1 pN0-1mi M0, grade 1–2, non-lobular breast cancer without the presence of extensive intraductal component and resected with negative margins were randomized after BCS to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 × 5.2 Gy high-dose-rate (HDR) multi-catheter brachytherapy (BT; n = 88) or 50 Gy electron beam (EB) irradiation (n = 40). Primary endpoint was local recurrence (LR) as a first event. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and cosmetic results.

Results

After a median follow up of 10.2 years, the ten-year actuarial rate of LR was 5.9% and 5.1% in PBI and WBI arms, respectively (p = 0.77). There was no significant difference in the ten-year probability of OS (80% vs 82%), CSS (94% vs 92%), and DFS (85% vs 84%), either. The rate of excellent-good cosmetic result was 81% in the PBI, and 63% in the control group (p < 0.01).

Conclusions

Partial breast irradiation delivered by interstitial HDR BT or EB for a selected group of early-stage breast cancer patients produces similar ten-year results to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with HDR BT implants compared with the outcome after WBI.     

Nuclear and cytoplasmic cellular distribution of survivin as survival predictor in resected non-small-cell lung cancer

Aim

Survivin is a member of the inhibitors of apoptosis (IAP) gene family that acts through pathways different from those involving the bcl-2 family. Largely undetectable in normal adult tissues, survivin is deregulated in most human cancers including non-small-cell lung cancer (NSCLC) and may represent a tumor marker with prognostic and therapeutic implications. Aim of our study was to determine the prognostic role of survivin as an apoptosis-related biomarker in a series of resected NSCLC patients.

Methods

A retrospective series of resected NSCLC patients were retrieved from the files of the Regina Elena National Cancer Institute. Survivin was detected by immunohistochemistry (IHC) using a polyclonal antibody. Survivin displayed two kinds of immunoreactivity: (i) a diffuse cytoplasmic staining and (ii) a distinct nuclear staining. A score-scale to distinguish positive (score 1–2) vs. negative (score 0) pattern was applied. Clinical and biological (nuclear and cytoplasmic survivin staining) covariables were screened for a prognostic relationship with overall survival (OS) and disease-free survival (DFS) into the univariate and multivariate analyses.

Results

Data referring to 116 NSCLC patients who underwent surgery for stage I–IIIA NSCLC were collected. Multivariate analyses identified tumor size, nodal status and nuclear, but not cytoplasmic, expression of survivin as significant independent predictors of OS, with a hazard ratio of 2.40 (95% CI 1.44, 3.99, p = 0.001), 2.03 (95% CI 1.26, 3.26, p = 0.003) and 1.83 (95% CI 1.01, 3.30, p = 0.044), respectively. Median OS for nuclear survivin positive (score 1–2) and negative (score 0) patients were 23 months (95% CI 15, 31) and 36 months (95% CI 1, 76), respectively (p = 0.01); five-year survival for score 1–2 and score 0 patients were 20% and 44.5%, respectively. Conversely, no significant impact on survival is found when patients are stratified according to cytoplasmic survivin expression.

Conclusions

Data presented herein open the issue that prognosis of stage I–IIIA NSCLC can be linked to the cellular pattern of distribution of survivin.     

Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma

Background

The 7th American Joint Committee on Cancer (AJCC) currently classifies combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) into one category. Study outcomes comparing the two carcinomas have shown contrary results. This study was designed to compare the survival and prognostic factors of both carcinomas.

Methods

We retrospectively reviewed the medical records of 107 patients with cHCC-CC or ICC who underwent liver resection between January 2000 and December 2009.

Results

Thirty patients (28%) were diagnosed with cHCC-CC, and 77 patients (72%) had ICC. Disease-free survival (DFS) was poorer in the cHCC-CC patients (six months), and the overall survival (OS) durations were similar (p = 0.477) between cHCC-CC (58 months) and ICC (45 months) patients. A tumor size larger than 5 cm, vascular invasion and lymph node (LN) metastasis were prognostic factors in all patients. However, tumor size and LN metastasis in cHCC-CC patients and carbohydrate antigen 19-9, differentiation and LN metastasis in ICC patients were found to be independent prognostic factors.

Conclusions

Patients with cHCC-CC showed poorer DFS and similar OS rates compared to those with ICC. Our study revealed different prognostic factors in cHCC-CC. To understand more accurately cHCC-CC's prognosis, difference of genetic characteristics and tumor biology should be further evaluated.     

14-3-3σ Expression and prognostic value in patients with epithelial ovarian carcinoma: A high throughput tissue microarray analysis

Aims

14-3-3σ is a potential tumor suppressor gene that when it is silenced by CpG methylation can contribute to cancer development. Previously, we showed that hypermethylation of 14-3-3σ in human ovarian cancer and ovarian cancer cell lines, and that 14-3-3σ hypermethylation correlated with loss of its expression by immunohistochemistry. In the present study, our aim is to determine the value of 14-3-3σ in predicting disease outcome in series of patients with epithelial ovarian cancer.

Materials and methods

A tumor microarray (TMA) of 192 patients with a very detailed characteristic and follow-up was performed. The slides were immunostained with 14-3-3σ antibody and its expression was correlated with age, tumor types, grade, stage, volume of residual tumor, response to therapy, overall survival (OS) and disease-free survival (DFS).

Results

A marginal association with the volume of residual tumor after surgery (chi2 p = 0.044, Fischer's exact 0.051) was seen. There was no association between loss of 14-3-3σ expression and any of age, stage, grade, tumor subtypes, and clinical response to therapy. Survival analysis according to Kaplan–Meier method showed that loss of 14-3-3σ expression was not associated with OS or DFS (p = 0.702, p = 0.118, respectively).

Conclusion

Even though 14-3-3σ is involved in ovarian tumorigenesis, it does not have a prognostic value as a biomarker to predict patients' outcome.     

Stereotactic Ablative Radiotherapy for stage I histologically proven non-small cell lung cancer: An Italian multicenter observational study

Objectives

Aim of this retrospective multicenter observational study was to provide data on outcomes and prognostic factors in patients affected with stage I histologically confirmed NSCLC treated with Stereotactic Ablative Radiotherapy (SABR, or Stereotactic Body Radiotherapy, SBRT) outside clinical trials.

Materials and Methods

We analyzed a cohort of 196 patients with histological/cytological diagnosis of NSCLC. Median age at treatment was 75 years old; median tumor diameter was 2.48 cm, and median GTV 13.3 cc. One hundred fifty-five patients had stage IA disease (79.1%) and 41 patients stage IB disease (20.9%). Total doses ranged from 48 to 60 Gy in 3–8 fractions. Primary endpoints of the study were safety (acute and late toxicity) and efficacy (Local Control, Disease-Free Survival, Overall and Cancer-Specific Survival).

Results

Median follow-up time was 30 months. The percentage of grade ≥2 pulmonary toxicity was 3%, and the 30 and 60 days mortality rate was 0%. Local Recurrence-Free Survival was 89.7% at 3 years. Fifty-nine patients (30.1%) had at least one failure (local and/or nodal and/or distant), with a Disease-Free Survival (DFS) rate at 3 years of 65.5%. Overall Survival (OS) and Cancer-Specific Survival (CSS) rates were 68% and 82.1% at 3 years, respectively. Median time to any recurrence was 15 months, while median overall survival time was 54 months. At multivariate analysis, stage IB was the only variable associated to a decrease in DFS, OS and CSS (HR 2.77, p = 0.006; HR 2.38, p = 0.009; HR 4.06, p ≤ 0.001, respectively). A difference in survival according to stage was also evident at the log-rank test (p ≤ 0.0001 for CSS and OS).

Conclusion

The results of the present study support the routine use of SABR for stage I NSCLC in a daily practice environment. The only prognostic factor that has been confirmed by our analysis was tumor stage (IA vs. IB).     

The presence of extrathoracic metastasis is more prognostic of survival than Masaoka stage (IVa/IVb) in metastatic thymic epithelial tumor: A retrospective cohort study

Purpose

Our aim in this study was to identify independent prognostic factors for overall survival (OS) in order to explain the heterogeneity of OS in patients with metastatic thymic epithelial tumor (TET).

Methods

Sixty-one consecutive patients with histologic diagnosis of Masaoka stage IV TET between January 1980 and March 2009 were analyzed at a single institution. Masaoka stage IVa was defined as pleural or pericardial dissemination, and IVb as lymphogenous or hematogenous metastasis. Metastasis outside the thoracic cage was defined as extrathoracic metastasis. To identify prognostic factors, relationships between clinicopathologic factors and outcomes were analyzed.

Results

Of the 61 patients, 30 (49.2%) had thymoma, 28 (45.9%) had thymic carcinoma, and the remaining 3 (4.9%) had an unclear histologic subtype. The Masaoka stage was IVa in 27 patients (44.3%) and IVb in 34 patients (55.7%). Significant independent adverse prognostic factors for OS were histologic subtype and extrathoracic metastasis (hazard ratio [HR] = 3.09 and 6.03, 95% CI: 1.41–6.74 and 1.89–19.30, p = 0.005 and 0.002, respectively). The presence of extrathoracic metastasis was also an independent prognostic factor for decreased progression-free survival time (PFS) (HR = 6.62, 95% CI: 1.19–24.17, p = 0.004). The only significant criterion for prognostic discrimination was the presence of extrathoracic metastasis in metastatic TET.

Conclusions

Significant independent prognostic factors for lower OS were the histologic subtype of thymic carcinoma and the presence of extrathoracic metastasis. A new concept of extrathoracic metastasis might provide additional information for the understanding of metastatic TET.     

A genetic sequence variant (GSV) at susceptibility loci of 5p15.33 (TERT-CLPTM1L) is associated with survival outcome in locally advanced and metastatic non-small-cell lung cancer (NSCLC)

Introduction

Lung cancer is a leading cause of cancer-related mortality in North America. In addition to tobacco smoking, inherited genetic factors can also influence the development of lung cancer. These genetic factors may lead to biologically distinct subsets of cancers that have different outcomes. We evaluated whether genetic sequence variants (GSVs) associated with lung cancer risk are associated with overall survival (OS) and progression-free survival (PFS) in stage-III-IV non-small-cell lung cancer (NSCLC) patients.

Methods

A total of 20 candidate GSVs in 12 genes previously reported to be associated with lung cancer risk were genotyped in 564 patients with stage-III or IV NSCLC. Multivariate Cox proportional hazard models adjusted for potential clinical prognostic factors were generated for OS and PFS.

Results

After taking into account multiple comparisons, one GSV remained significant: rs4975616 on chromosome 5p15.33, located near the TERT-CLPTM1L gene. The adjusted hazard ratio (aHR) for OS was 0.75 (0.69–0.91), p = 0.002; for PFS aHR was 0.74 (0.62–0.89), p < 0.001 for each protective variant allele. Results were similar in both Stage III (OS: aHR = 0.70; PFS: aHR = 0.71) and Stage IV patients (OS: aHR = 0.81; PFS: aHR = 0.77).

Conclusion

A GSV on 5p15.33 is not only a risk factor for lung cancer but may also be associated with survival in patients with late stage NSCLC. If validated, GSVs may define subsets of patients with different risk and prognosis of NSCLC.     

Outcomes for a large series of radical cystectomies for bladder cancer

Aims

We present the characteristics and outcomes of a large Chinese series of patients treated with radical cystectomy and pelvic lymphadenectomy for invasive cancer of the bladder. Our aim is to determine the significant independent prognostic factors that determine this outcome.

Methods

The records of 356 patients with invasive bladder cancer, operated at three Chinese medical institutes between 1995 and 2004, were reviewed. Of the 356 patients, 324 (91.0%) were TCC, 24 (6.7%) were adenocarcinoma, eight (2.3%) were squamous carcinoma. The incidence of pelvic lymph node involvement was 22.8%. The mean (SD, range) follow-up of the 356 patients was 54.89 (31.66, 3–137) months. Multivariate analysis was used to assess the clinical and pathological variables affecting disease-free survival (DFS).

Results

The 1-, 2- and 5-year DFS rates were 87%, 75% and 48%, respectively. In multivariate analysis, tumor configuration (RR = 1.62, p = 0.012), multiplicity (RR = 1.41, p = 0.036), histological subtype (RR = 2.17, p < 0.001), tumor stage (RR = 2.50, p < 0.001), tumor grade (RR = 2.40, p < 0.001), node status (RR = 2.51, p < 0.001), neoadjuvant chemotherapy (RR = 0.46, p = 0.016) had independent significance for survival on multivariate analysis.

Conclusions

The results of this series show that radical cystectomy and pelvic lymphadenectomy provide durable local control and DFS in patients with invasive bladder cancer. Multivariates affect the prognosis after radical cystectomy for invasive bladder cancer. The treatment of invasive bladder cancer in China is still in need of improvement and normalization.     

Lower uterine segment involvement is associated with adverse outcome in patients with stage I endometroid endometrial cancer: Results of a multicenter study

Objective

To quantify the relative risk associated with lower uterine segment involvement (LUSI) on outcome measures in patients with apparent stage I endometroid endometrial cancer.

Methods

A cohort of 769 consecutive patients with endometroid endometrial carcinoma apparent stage I, who underwent surgery in five gynecological oncology centers in Israel; 138 patients with and 631 without LUSI were followed for a median time of 51 months. Local recurrence, recurrence-free and overall survival were compared between the two groups.

Results

LUSI was associated with grade 3 tumor (p = 0.002), deep myometrial invasion (p < 0.001), and the presence of lymphvascular space involvement (p = 0.01). There were 22 cases of local recurrences, 40 cases of distal recurrences and 80 patients died. Univariate survival analysis showed that patients with LUSI had trend toward lower regional recurrence-free survival (p = 0.09), and significant lower distant recurrence-free survival (p = 0.04) and lower overall survival (p = 0.002). The Cox proportional hazards model demonstrated a significantly decreased overall survival (HR = 2.3; 95% CI 1.3, 3.9; p = 0.003) in cases with LUSI.

Conclusions

In patients with apparent stage I endometroid endometrial cancer, the presence of LUSI is a poor prognostic factor, associated with a significantly higher risk of distal recurrence and death. The presence of LUSI warrants consideration when deciding upon surgical staging or postoperative management.     

‘Close Shave’ in liver resection for colorectal liver metastases

Introduction

The optimal size of clear liver resection margin width in patients with colorectal liver metastases (CRLM) remains controversial. The aim of this study was to investigate the effects of margin width on long-term survival after liver resection for CRLM with a policy of standard neo-adjuvant chemotherapy.

Methods

Consecutive patients (n = 238) who underwent liver resection for CRLM were included over a ten-year period. All patients with synchronous or early (<2 years) metachronous tumours were treated with neo-adjuvant chemotherapy. Data were recorded prospectively.

Results

Overall survival of the cohort at 1, 3 and 5 years were 90.3%, 68.1% and 56.1% respectively. The incidence of cancer involved resection margins (CIRM) was 5.8%. Patients with macroscopically involved resection margins had a poorer overall survival than those with microscopically involved margins (p = 0.04). Involved resection margins had a poorer overall survival (p = 0.002) than patients with clear margins. Width of clear resection margin did not affect long-term survival.

Conclusion

CIRM independently predicts poor outcome in patients with CRLM. Clear margin width does not affect survival. A standard policy of neo-adjuvant chemotherapy may be associated with a low incidence of CIRM and improved long-term outcome of sub-centimetre margin widths, resembling those with >1 cm resection margins.     

HDR brachytherapy combined with interstitial hyperthermia in locally advanced cervical cancer patients initially treated with concomitant radiochemotherapy – a phase III study

Background and purpose

The aim of this randomised trial was to investigate whether hyperthermia (HT) combined with interstitial brachytherapy (ISBT) has any influence on local control (LC), disease-free survival (DFS), or acute and late side effects in patients with advanced cervical cancer.

Materials and methods

After radiochemotherapy, consecutive patients with cervical cancer (FIGO stage II–III) were randomly assigned to two treatment groups, either ISBT alone or ISBT combined with interstitial hyperthermia (ISHT). A total of 205 patients were included in the statistical analysis. Once a week, HT, at a temperature above 42.5 °C, was administered for 45 min before and during the HDR BT.

Results

The median follow-up time was 45 months (range 3–72 months). An effect of hyperthermia was not detected for disease-free survival (DFS) (log-rank test: p = 0.178) or for local control (LC) (p = 0.991). According to Cox’s analysis, HT did not significantly influence failure or interactions with potential prognostic factors for LC or DFS. Statistical differences were not observed for the distribution of early and late complications between the HT and non HT groups.

Conclusions

ISHT is well-tolerated and does not affect treatment-related early or late complications. Improvements in DFS and LC were not observed following the addition of ISHT to ISBT.