Histopathologic analysis of stage pT1b kidney neoplasms for optimal surgical margins of nephron-sparing surgery

Objective

To evaluate the pathological features and define the optimal surgical margins (SM) of nephron-sparing surgery (NSS) for kidney neoplasms 4–7 cm (stage pT1b) on preoperative imaging.

Materials and methods

The retrospective study included 748 patients who were diagnosed stage pT1b renal tumors and underwent either radical nephrectomy (RN, n = 475) or NSS (n = 273) from January 2004 to March 2017. The tumor size, pathological subtype, Fuhrman grade, status of peritumoral pseudocapsule (PC) and tumor multifocality were recorded. The relationship between peritumoral PC and positive SM was calculated statistically by Fisher’s exact probability test.

Results

The mean tumor diameter was 5.4 cm (range: 4.1–7.0 cm), 65 (8.7%) cases were discovered with multifocal lesions and 686 (91.7%) were surrounded with peritumoral PC in all 748 specimens. 57 (8.3%) of 686 cases were proved with tumor infiltrated beyond PC [infiltration (+)], and the presence of PC infiltration (+) was significantly correlated with positive SM (p = 0.016). The infiltrative depth of tumor cells into renal parenchyma beyond PC was all limited in 3 mm and the proportion of ≤ 1, 1–2 and 2–3 mm was 21.1% (12/57), 59.6% (34/57) and 19.3% (11/57), respectively.

Conclusions

Our report indicates a 3 mm excisional margin is acceptable to ensure negative SM when operating NSS on stage pT1b kidney neoplasms.

     

Limited benefit of targeted molecular therapy for inferior vena cava thrombus associated with renal cell carcinoma

Background

The clinical benefit of targeted molecular therapy (TMT) for an inferior vena cava (IVC) tumor thrombus associated with renal cell carcinoma (RCC) is unclear. The aim of the present study was to assess the change in IVC thrombus height during TMT and to identify the factors associated with the effect of TMT on an IVC thrombus in RCC patients.

Methods

The present study retrospectively analyzed 21 patients with an IVC thrombus who were treated with TMT at our hospital. Thrombus height and level before and after TMT were assessed using CT or MRI. Furthermore, we examined the factors associated with the effect of TMT on the IVC thrombus.

Results

The tumor thrombus level before TMT was I in 2 patients (10%), II in 10 (47%), III in 4 (19%), and IV in 5 (24%). Following TMT, the tumor thrombus height decreased in 16 patients (76%), and the mean decrease was 17 mm. The tumor thrombus height increased in 5 patients (24%), and the mean increase was 30 mm. The tumor thrombus level decreased in 4 patients (19%), remained stable in 15 patients (71%), and increased in 2 patients (10%). We found that the clinical nodal stage (p = 0.025) was significantly associated with and the serum neutrophil count (p = 0.067) tended to be associated with the reduction in the IVC thrombus.

Conclusion

The clinical benefit of TMT for an IVC thrombus associated with RCC is limited.

     

Association of decreased mean platelet volume with renal cell carcinoma

Background

Renal cell carcinoma (RCC) is the third most common genitourinary cancer. Activated platelets play a pivotal role in cancer development and progression. Altered mean platelet volume (MPV) has been reported in several malignancies. The aim of the present study was to investigate the association of MPV with RCC.

Study design

The study consisted of 145 patients with RCC, 110 patients with benign renal tumor and 132 healthy control subjects between January 2015 and December 2015. All participants’ clinical and laboratory characteristics at initial diagnosis were collected. The odds ratios (ORs) for RCC were calculated using multivariate logistic regression analysis after adjusting for confounding variables across MPV quartiles.

Results

The patients with RCC had decreased pre-operative MPV compared to the patients with benign renal tumor and healthy control subjects. Furthermore, pre-operative MPV was reduced in benign renal tumor compared with healthy control subjects. Surgical tumor resection resulted in a significant increase in MPV levels (8.7 fL vs. 9.0 fL; p = 0.011). After adjusting for other risk factors, the ORs (95% CIs) for RCC in each MPV quartile were 25.725 (7.556–87.585), 7.447 (2.701–20.537), 0.703 (0.245–2.019), and 1.000, respectively.

Conclusions

RCC patients have remarkably reduced MPV compared to patients with benign renal tumor and healthy control subjects. Moreover, decreased MPV was independently associated with RCC. Our results suggest that detection of MPV may be useful to assess the risk of RCC.

     

Low preoperative serum cholesterol level is associated with aggressive pathologic features and poor cancer-specific survival in patients with surgically treated renal cell carcinoma

Background

The prognostic implications of preoperative serum total cholesterol (TC) level in patients with renal cell carcinoma (RCC) remain poorly understood. We investigated the prognostic role of preoperative serum TC in patients with surgically treated RCC from a large, multi-institutional Korean collaboration.

Patients and methods

A database of 3064 patients with RCC who underwent radical or partial nephrectomy between 1999 and 2011 at eight academic centers was analyzed. Preoperative serum TC levels were measured in fasting blood samples.

Results

Low preoperative serum TC level was associated with aggressive tumor characteristics, including large tumor size, advanced stage, high nuclear grade, lymph node involvement, and sarcomatous differentiation (all P < 0.001). Low TC level was associated with poor recurrence-free or cancer-specific survival (CSS) in the entire cohort, whereas the significance of the association changed after stratification by disease stage and histologic subtype. Multivariate Cox regression analysis showed that preoperative TC, as a continuous or categorical variable, was an independent predictor of CSS.

Conclusions

Preoperative low serum TC level was associated with aggressive tumor characteristics and poor CSS in patients with surgically treated RCC. Preoperative TC may provide additional guidance regarding the choice of therapeutic strategies to improve prognosis.

     

MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case–control study

Purpose

Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer.

Methods

Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical–pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical–pathologic features was assessed using Cox proportional hazard models.

Results

Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages.

Conclusion

Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

     

Salvage treatment with irinotecan/cisplatin versus pemetrexed/cisplatin in patients with non-small cell lung cancer pre-treated with a non-platinum-based regimen in the first-line setting: a randomized phase II study of the Hellenic Oncology Research Group (HORG)

Background

Platinum-based chemotherapy is the standard front-line treatment for patients with advanced non-small cell lung cancer (NSCLC). However, non-platinum combinations of third-generation chemotherapeutic agents are considered an alternative therapeutic option for patients who cannot tolerate the toxic effects of platinum compounds. In this study, the efficacy and toxicity of the combination of irinotecan plus cisplatin (IC) was compared to pemetrexed plus cisplatin (PC) regimen, in platinum-naïve patients with advanced NSCLC, who had been previously treated with the combination of a taxane plus gemcitabine.

Patients and methods

A total of 124 patients with locally advanced or metastatic NSCLC were randomly assigned to either irinotecan 110 mg/m² on day 1 and 100 mg/m² on day 8 plus cisplatin 80 mg/m² on day 8 every 3 weeks (IC arm) or pemetrexed 500 mg/m² plus cisplatin 80 mg/m² on day 1 every 3 weeks (PC arm). The primary endpoint of the study was the overall response rate (ORR).

Results

The ORR and median progression-free survival (PFS) in the IC arm were 18 % and 3.3 months, respectively, while in the PC arm were 19 % and 4.2 months (p = ns). Median overall survival (OS) was significantly higher in patients with PC (6.9 vs. 10.9; p = 0.013). PC regimen had a better toxicity profile compared to IC, with a statistically significant lower incidence of grade 3/4 neutropenia (3 vs. 31 %; p = 0.0001) and diarrhea (1.6 vs. 14.7 %, p = 0.018).

Conclusions

In patients with advanced NSCLC pretreated with docetaxel/gemcitabine, the combination of pemetrexed/cisplatin is associated with increased OS and is better tolerated than the combination of irinotecan/cisplatin and should be considered as a valid therapeutic option for platinum-naive, previously treated patients.

ClinicalTrials.gov Identifier

NCT00614965.

     

A Randomized,Open-Label Phase 2 Study of the CXCR4 Inhibitor LY2510924 in Combination with Sunitinib Versus Sunitinib Alone in Patients with Metastatic Renal Cell Carcinoma (RCC)

Purpose

The chemokine (C-X-C Motif) receptor 4 (CXCR4) and its ligand, stromal-cell derived factor-1 (SDF-1), are frequently overexpressed in a variety of solid tumors, and are believed to play important roles in the regulation of organ-specific metastasis, tumor growth, invasion, and survival. In this randomized Phase 2 trial, we evaluated the safety and efficacy of LY2510924 (LY), a peptide antagonist of CXCR4, combined with sunitinib (SUN) in the first-line treatment of advanced renal cell carcinoma (RCC).

Patients and Methods

Eligible patients were randomized (2:1) to receive LY (20 mg SC daily) + SUN (50 mg PO daily for 4 weeks followed by 2 weeks off) or SUN alone. Response was assessed after two cycles; patients continued treatment until tumor progression or intolerable toxicity. The study was powered to detect a 47 % increase in median progression-free survival (PFS).

Results

One hundred eight patients were randomized and treated (LY + SUN, 72; SUN, 36); median duration of treatment of five cycles. Observed median PFS was 8.1 months with LY + SUN and 12.3 months with SUN; Bayesian time-to-event HR 1.23; 95 % credible interval: 0.74, 1.96. LY was well tolerated; the toxicity profile was typical of SUN. No efficacy differences were seen between treatments groups when subsets with high versus low levels of CXCR4 tumor expression were compared.

Conclusions

The addition of LY to SUN in the first-line treatment of metastatic RCC was well tolerated, but did not improve the PFS or overall survival (OS) vs. SUN alone. CXCR4 remains an unproven therapeutic target for the treatment of RCC.

Clinical Trial.gov Identifier

NCT01391130

Open image in new window

     

Breast cancer in elderly women and altered clinico-pathological characteristics: a systematic review

Purpose

Breast cancer is the most common malignancy in women in terms of incidence and mortality. Age is undoubtedly the biggest breast cancer risk factor. In this study we examined clinical, histological, and biological characteristics and mortality of breast cancer in elderly women along with their changes with advancing age.

Methods

We reviewed 63 original articles published between 2006 and 2016 concerning women over 70 years with breast cancer.

Results

Compared to patients 70–79 years, patients aged 80 and over had larger tumor size with fewer T1 (42.9% vs 57.7%, p < 0.01) and more T2 lesions (43.5% vs 33.0%, p < 0.01). Lymph nodes and distant metastases were more frequent, with more N + (49.5% vs 44.0%, p < 0.01) and more M1 (8.0% vs 5.9%, p < 0.01). Infiltrating mucinous carcinomas were more frequent (4.3% vs 3.7%, p < 0.01). Tumors had lower grades, with more grade 1 (23.2% vs 19.8%, p = 0.01) and fewer grade 3 (21.5% vs 25.5%, p < 0.01), and were more hormone-sensitive: PR was more often expressed (72.6% vs 67.3%, p < 0.01). Lympho-vascular invasion was less frequent in the 80 years and over (22.9% vs 29.7%, p = 0.01). Breast cancer-specific mortality was higher both at 5 years (25.8% vs 17.2%, p < 0.01) and 10 years (32.7% vs 26.6%, p < 0.01).

Conclusion

Clinico-pathological characteristics, increased incidence, and mortality associated with aging can be explained on one hand by biological changes of the breast such as increased estrogen sensitivity, epithelial cell alterations, immune senescence, and tumor microenvironment modifications. However, sociologic factors such as increased life expectancy, under-treatment, late diagnosis, and insufficient individual screening, are also involved.

     

Pre-treatment mean platelet volume associates with worse clinicopathologic features and prognosis of patients with invasive breast cancer

Background

Mean platelet volume (MPV) is one of the four platelet parameters (platelet count, MPV, platelet distribution width and plateletcrit), which indicates the activation of platelet. We aim to investigate the associations between pre-treatment MPV levels and clinical hematology parameters, pathology parameters and prognosis of patients with invasive breast cancer (IBC).

Methods

Medical records of 340 breast tumor patients (170 IBC vs. 170 breast benign tumor) were retrospectively reviewed. Patients in two groups were matched for age, body mass index, smoking status and complications. To analyze: differences in pre-treatment MPV levels between IBC group and breast benign tumor group; differences between pre- and postoperative MPV levels in IBC patients; correlations between pre-treatment MPV and clinical hematology parameters, clinicopathologic parameters and prognosis in IBC patients.

Results

As we analyzed, pre-treatment MPV levels of IBC patients were significantly higher than the controls (8.65 ± 0.98 vs 8.34 ± 0.78, P = 0.002), and preoperative MPV levels were significantly higher than the postoperative in IBC patients (8.65 ± 0.98 vs 8.44 ± 0.91, P = 0.042). In IBC group, pre-treatment MPV level associated, significantly, with clinical hematology parameters (platelet, fibrinogen, albumin, fasting blood glucose, P = 0.003, 0.042, 0.032, 0.046, respectively) and with clinicopathological parameters (distant metastasis, primary tumor size, tumor node metastasis stages, P = 0.039, 0.002, 0.001, respectively). Furthermore, univariate and multivariate survival analysis demonstrated that MPV was significant prognostic factor (P = 0.035, HR 1.86, 95 % confidence interval 1.06–3.25).

Conclusion

High pre-treatment MPV level in IBC patients was a potential predictive factor and significant independent prognostic factor.

     

Prostate cancer-related anxiety in long-term survivors after radical prostatectomy

Purpose

Knowledge of the psychological distress of long- and very long-term (>10 years) prostate cancer (PC) survivors is limited. This study intended to examine the parameters influencing anxiety related to prostate-specific antigen (PSA) and PC in long-term survivors after radical prostatectomy.

Methods

We surveyed 4719 PC survivors from the German multicenter prospective database “Familial Prostate Cancer.” We evaluated the association of PC-related anxiety (MAX-PC) with sociodemographic characteristics, family history of PC, global health status/quality of life (EORTC QLQ-C30), depression and anxiety (PHQ-2; GAD-2), latest PSA level, time since radical prostatectomy, and current therapy.

Results

The survey participants’ mean age was 75.2 years (SD = 6.5). Median follow-up was 11.5 years, and 19.5% of participants had survived more than 15 years since the initial treatment. The final regression analysis found that younger age, lower global health status/quality of life, higher depression and anxiety scores, higher latest PSA level, and shorter time since radical prostatectomy predicted increased PSA-related anxiety and PC anxiety. Familial PC was predictive only of PSA anxiety (all p < 0.05). The final model explained 12% of the variance for PSA anxiety and 24% for PC anxiety.

Conclusions

PC-related anxiety remained relevant many years after prostatectomy and was influenced by younger age, psychological status, rising PSA level, and shorter time since initial treatment.

Implications for Cancer Survivors

Survivors with these characteristics are at increased risk of PC-related anxieties, which should be considered by the treating physician during follow-up.

     

Do patients whose tumor achieved a pathological response relapse at specific sites? A substudy of the EORTC 10994/BIG-1-00 trial

Purpose

To determine the sites of first distant relapse in patients with or without pCR following neoadjuvant chemotherapy in breast cancer patients enrolled in the EORTC 10994/BIG-1-00 trial.

Methods

We included patients enrolled in the EORTC 10994/BIG-1-00 trial who received at least one chemotherapy cycle before surgery and who had been diagnosed with a distant relapse. pCR was defined as no evidence of residual invasive cancer in the primary tumor and axillary lymph nodes with or without residual ductal carcinoma in situ. Site of first distant relapse was categorized as ‘soft tissue,’ ‘visceral,’ ‘skeletal,’ ‘central nervous system (CNS),’ and ‘other.’ The association between relapse site and achievement of pCR was assessed using multivariate logistic regression models for molecular subtypes classification and preceding locoregional recurrence.

Results

The study included 383 (21%) eligible patients out of the 1856 randomized, of whom 28 (7%) had achieved pCR. Median follow-up was 5.4 years. Achievement of pCR was associated with a trend towards a decreased presentation of skeletal metastases [21% (pCR) vs. 50% (non-pCR), OR 0.32, adjusted p value = 0.071] and an increase in the proportion of patients with CNS metastases as first distant relapse site (21% vs. 9%, OR 2.39, adjusted p value = 0.183). Patients with pCR were more likely to present with only one relapse location category when compared to non-pCR (86% vs. 69%).

Conclusion

Patients that achieved a pCR appeared less likely to present with skeletal metastases and more frequently presented with CNS metastases as first site of distant relapse, even after adjustment for molecular subtypes.

     

Elevated Syndecan-1 levels in the sera of patients with breast cancer correlate with tumor size

Background

Breast cancer is the leading type of cancer in Iranian women and affects them at least one decade younger than their counterparts in developed countries. Breast tumor progression and metastasis is accompanied by a decrease in the membranous expression of Syndecan-1 and an increase in its shedding. We measured the level of soluble Syndecan-1 in the sera of Iranian patients with breast cancer.

Methods

The study population included 61 chemotherapy-naïve breast cancer patients and 30 age/sex-matched healthy individuals. Blood was collected by venipuncture method and serum was separated, aliquoted and kept at ?40 °C until used. A commercial ELISA was used to detect Syndecan-1 levels in the sera.

Results

Soluble Syndecan-1 levels were increased in the sera of patients with breast cancer compared to healthy controls (87.89 ± 89.29 vs. 47.57 ± 46.46 ng/ml, p = 0.005). There was a positive correlation between soluble Syndecan-1 levels and tumor size (p = 0.017). The serum level of Syndecan-1 in patients without calcification showed a trend of increase compared to that of patients with calcification (108.80 ± 101.76 vs. 59.82 ± 57.13 ng/ml).

Conclusion

The positive correlation between soluble Syndecan-1 levels and tumor size in the present study highlights the importance of different varieties (cell-bound and soluble) of this molecule in the breast tumor progression and their significance as tumor biomarkers.

     

Ultrasound findings and histological features of ductal carcinoma in situ detected by ultrasound examination alone

Background

With the increasing use of high-resolution ultrasound (US) examination, many breast carcinomas that cannot be identified by mammography (MMG) alone have been detected. Many of these carcinomas are ductal carcinoma in situ (DCIS) and small-sized invasive carcinomas. Until date, DCISs have often been described as palpable masses with calcifications on MMG, but what are the characteristics of DCISs that are detectable by US alone?

Methods

One hundred fifty cases with DCIS that we experienced at our clinic from 2003 to 2007 were classified into 47 cases (echo group) diagnosed by US alone and 103 cases (MMG/PE group) diagnosed by MMG or clinically.

Results

US findings of the echo group showed cystic or solid lesions in 37 cases (79%). The mean age of the echo group was significantly higher than that of the MMG/PE group (59.6 vs. 51.2 years; P < 0.01). Tumor sizes detected by US were 5.7 + 2.8 and 11.5 + 10.8 mm (P < 0.001), respectively. The tumor sizes of the echo group were, therefore, approximately half that of the MMG/PE group. Extensive intraductal components were significantly fewer in the echo group, and tumor grades of the echo group were significantly low (Van Nuys classification). In the echo group, all cases with a tumor size <5 mm were grade 1 by Van Nuys classification. In addition, cases with ≥5 mm tumor size had a significantly lower tumor grade in the echo group than in the MMG/PE group.

Conclusions

Cystic or solid lesions accounted for approximately 80% of US findings of DCISs detected by US alone, and most were similar to benign forms. Moreover, most DCISs detected by US alone were localized and of low grade (Van Nuys classification).

     

Comparison of ILK and ERP29 expressions in benign and malignant pancreatic lesions and their clinicopathological significances in pancreatic ductal adenocarcinomas

Introduction

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant tumor of the pancreas with poor prognosis. The lack of understanding of the molecular mechanisms of PDAC and biomarkers for early diagnosis might be two of the reasons for the poor prognosis of PDAC.

Materials and methods

ILK and ERP29 protein expressions in PDAC, peritumoral tissues, benign pancreatic lesions, and normal pancreatic tissues were measured by immunohistochemistry and the clinical and pathological significances of ILK and ERP29 in PDAC were analyzed.

Results

The percentages of positive ILK and negative ERP29 expressions were significantly higher in PDAC tumors than in peritumoral tissues, benign pancreatic tissues, and normal pancreatic tissues (P < 0.01). Benign pancreatic lesions with positive ILK and negative ERP29 expressions exhibited dysplasia or intraepithelial neoplasia. The percentage of cases with positive ILK and negative ERP29 expressions was significantly lower in PDAC patients without lymph node metastasis and invasion, and having TNM stage I/II disease than in patients with lymph node metastasis, invasion, and TNM stage III/IV disease (P < 0.05 or P < 0.01). Kaplan–Meier survival analysis showed that positive ILK and negative ERP29 expressions were significantly associated with survival in PDAC patients (P < 0.001). Cox multivariate analysis revealed that positive ILK and negative ERP29 expressions were independent poor prognosis factors in PDAC patients.

Conclusions

Positive ILK and negative ERP29 expressions are associated with the progression of PDAC and poor prognosis in patients with PDAC.

     

Annual hazard rate of relapse of stage II and III colorectal cancer after primary therapy

Purpose

To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features.

Methods

We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups.

Results

Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1–2] year-interval by 10.1% and [3–4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1–2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1–4, in colon cancer and in stage III but without impact in rectal cancer and stage II.

Conclusion

Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series.

     

Presurgical axitinib therapy increases fibrotic reactions within tumor thrombus in renal cell carcinoma with thrombus extending to the inferior vena cava

Background

Clinical benefits of presurgical axitinib therapy for renal cell carcinoma (RCC) extending into the inferior vena cava (IVC) remain unclear. We aimed to investigate surgical benefits and pathological antitumor effects of presurgical axitinib therapy for RCC with IVC thrombus.

Methods

Of 56 consecutive RCC patients with IVC thrombus between January 1994 and December 2016, 41 patients who underwent radical nephrectomy (RN) were categorized as upfront RN (Upfront group) or presurgical axitinib followed by RN (Presurgical group). We retrospectively evaluated safety, radiologic tumor responses, and Ki-67 proliferation index before and after axitinib administration in the Presurgical group. Surgical outcomes, postoperative complications, and fibrosis within the IVC thrombus were compared between the Upfront and Presurgical groups.

Results

The number of patients in the Upfront and Presurgical groups was 31 and 10, respectively. Major presurgical axitinib-related adverse events were grade 2 or 3 hypertension (50%). The median radiological tumor response in the renal tumor, IVC thrombus length, and IVC thrombus volume were ?19%, ?21 mm, and ?54%, respectively. The fibrosis within the IVC thrombus was significantly higher in the Presurgical group (10%) than in the Upfront group (3.4%). The Ki-67 proliferation index was significantly decreased in RN specimens (7.3%) versus needle biopsy specimens (23%) in the Presurgical group. Blood loss and operative duration were significantly lower and shorter, respectively, in the Presurgical group than in the Upfront group.

Conclusions

Presurgical axitinib therapy enhanced tumor reduction accompanied by fibrosis and may contribute to surgical risk reduction for selected patients.

     

Circulating levels of obesity-related markers and risk of renal cell carcinoma in the PLCO cancer screening trial

Purpose

Obesity is an established risk factor for renal cell carcinoma (RCC). It is unclear what biologic mechanisms underlie this association, although recent evidence suggests that the effects of circulating hormones such as insulin-like growth factors (IGF) and adipokines may play a role.

Methods

To address this question, we conducted a nested case–control study of RCC (252 cases, 252 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial investigating associations with pre-diagnostic serum levels of total adiponectin, high-molecular-weight (HMW) adiponectin, IGF-1, IGF-binding protein-3 (IGFBP-3), and C-peptide. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using conditional logistic regression.

Results

After adjustment for potential confounders, non-significant associations with RCC were observed for total adiponectin (OR for highest vs. lowest quartile = 0.65, 95% CI 0.37–1.14; p _trend = 0.35), HMW adiponectin (0.67, 0.38–1.17; p _trend = 0.36), IGF-1 (1.35, 0.77–2.39; p _trend = 0.17), IGFBP-3 (1.47, 0.83–2.62; p _trend = 0.53), and C-peptide (1.52, 0.86–2.70; p _trend = 0.15). In a joint analysis with body mass index (BMI, kg/m²), obese individuals (BMI ≥30) with above-median levels of IGFBP-3 had a significantly higher risk versus those with BMI <25 and below-median IGFBP-3 (OR 2.42, 1.11–5.26), whereas obese individuals with low IGFBP-3 did not (1.18, 0.53–2.64) (p _interaction = 0.35).

Conclusions

The results of this study, while not clearly supporting associations with these obesity-related hormones, suggest that the association between obesity and RCC may be partially modified through mechanisms related to elevated IGFBP-3.

     

Feasibility of analyzing DNA copy number variation in breast cancer tumor specimens from 1950 to 2010: how old is too old?

Purpose

The purpose of the study was to assess the feasibility of quantifying long-term trends in breast tumor DNA copy number variation (CNV) profiles.

Methods

We evaluated CNV profiles in formalin-fixed paraffin-embedded (FFPE) tumor specimens from 30 randomly selected Kaiser Permanente Northern California health plan women members diagnosed with breast cancer from 1950 to 2010. Assays were conducted for five cases per decade who had available tumor blocks and pathology reports.

Results

As compared to the tumors from the 1970s to 2000s, the older tumors dating back to the 1950s and 1960s were much more likely to (1) fail quality control, and (2) have fewer CNV events (average 23 and 31 vs. 58 to 69), fewer CNV genes (average 5.1 and 3.7k vs. 8.1 to 10.3k), shorter CNV length (average 2,440 and 3,300k vs. 5,740 to 9,280k), fewer high frequency Del genes (37 and 25% vs. 54 to 76%), and fewer high frequency high_Amp genes (20% vs. 56 to 73%). On average, assay interpretation took an extra 60 min/specimen for cases from the 1960s versus 20 min/specimen for the most recent tumors.

Conclusions

Assays conducted in the mid-2010s for CNVs may be feasible for FFPE tumor specimens dating back to the 1980s, but less feasible for older specimens.

     

Short stature in retinoblastoma survivors: a cross-sectional study of 138 patients

Purpose

Short stature has been reported in pediatric cancer survivors. Data on retinoblastoma survivors are limited. We conducted a cross-sectional study to assess the height in retinoblastoma survivors.

Method

The recorded height was compared with median height for age and sex as per the Indian Academy of Pediatrics. Z-score less than ?2 was considered short statured.

Result

Thirty percent of the survivors were short statured. The mean height was shorter than the mean 50th percentile height (119.7 ± 14.8 vs 128.7 ± 15 cm, p < 0.001). Previous chemotherapy showed a trend toward association (p = 0.09).

Conclusion

Short stature affects a significant number of retinoblastoma survivors.

     

Continued EGFR-TKI with concurrent radiotherapy to improve time to progression (TTP) in patients with locally progressive non-small cell lung cancer (NSCLC) after front-line EGFR-TKI treatment

Background

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment.

Methods

Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression. Medical data were analyzed for time to progression (TTP), progression-free survival (PFS), tumor response rate, overall survival (OS) and adverse events.

Results

A total of 50 irradiated lesions from 44 patients were included. Median TTP and PFS of measurable lesions (n = 31) were both significantly prolonged after local radiotherapy (TTP1 + TTP2 vs. TTP1: 21.7 vs. 16.0 months, P = 0.010; PFS1 + PFS2 vs. PFS1: 21.3 vs. 16.0 months, P = 0.027). For all lesions (n = 50), objective response rate (ORR) and local tumor control rate (LCR) were 54.0 and 84.0%, respectively. Median OS was 26.6 months. There were no serious adverse events before or after radiotherapy.

Conclusions

The treatment modality of CTCRT is considerable and effective for EGFR-mutant NSCLC patients even with local failure from front-line EGFR-TKI treatment.