Does the degree of cell lesion in breast cancer after inductive chemotherapy have any prognostic value?

During 1991 and 1992, 77 patients with breast cancer were treated with induction chemotherapy using the CMFV and FAC protocols at the Lublin Oncological Centre. The degree of cancer cell damage in the specimens obtained postoperatively was evaluated by microscopy. Complete or substantial damage of neoplastic cells was found in 29% of the cases; whereas minimal to no damage was found in 71% of specimens. After assessing the 5-year survival periods of our patients in relation to the degree of cancer cell damage after induction chemotherapy, a statistically significant correlation was noted. Five-year survival without cancer symptoms was observed in 64% of cases in which the cell damage was estimated as considerable, and only in 34% in which the damage was slight or not notable. A much weaker correlation was observed between the degree of breast cancer cell damage after inductive chemotherapy and clinical response.     

Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?

Medical Oncology - Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in...     

What is the real prognostic value of close margins in oral oncology?

Aim: The surgical margin is usually considered an important prognostic factor in oral oncology. However, the real value of a close surgical margin and its relationship with survival is still unclear. Thus, the present report sought to identify the relationship between close surgical margins and overall 3-year survival, whilst also analyzing the association between such margins and recurrence.Materials and Methods: The medical records of 200 patients affected by oral squamous cell carcinoma were retrospectively reviewed. The patients were divided into three groups: positive margin (0-2 mm), close margin (2-5 mm), and negative margin (>5 mm). The relationship between surgical margins and overall survival and recurrence rate was analyzed.Results: Surgical margins and reoperation were found to have no significant association with overall survival (P > 0.05). Overall survival was 63% in our sample. Specifically, this was 50%, 64.7% and 66.2% in patients with positive, close and free margins, respectively. Perineural invasion, pN, and locoregional or cervical recurrences were the factors most directly related to overall survival.Discussion: The results of this study indicate that surgical margins are not directly related to overall survival and other factors might significantly influence patient outcomes. Advanced T stage, node involvement, perineural invasion, and ECS are strongly linked with patient survival (P < 0.05). These findings should be carefully evaluated in patients with close surgical margins. Our results indicate that an aggressive adjuvant treatment of patients with close surgical margins could help in obtaining a similar pattern of overall survival with patients with negative margins.     

Does the expression of BCL2 have prognostic significance in malignant peritoneal mesothelioma?

Background Malignant peritoneal mesothelioma (MPM) is a rare neoplasm of the peritoneal membrane that is causally related to asbestos exposure. Survival after treatment is poor. Current therapy involving hyperthermic intraperitoneal chemotherapy has improved survival in selective patients. In the past, several prognostic factors have been identified in MPM patients and this has prompted the development of new therapies and patient management. Since BCL2, an antiapoptotic oncoprotein, is a favourable prognostic factor in breast cancer, we investigated to determine the significance of BCL2 in MPM. Materials and Methods Forty two archival patient tumour sections embedded in paraffin blocks were sectioned and subjected to immunohistochemistry to detect BCL2. The staining intensity and abundance was classified using standard procedures and classified into two groups (0-4 = low & 5-8 = high expression). The distribution of BCL2 groups was examined in the different clinicopathological categories to determine prognosis using Kaplan–Meier survival analysis. Results: Univariate analysis revealed that in almost all clinicopathological categories, high BCL2 expression predisposed patients to a favourable prognosis. Independent of BCL2 expression, univariate analysis also showed that male gender, sarcomatoid histology, high PCI and age at diagnosis ≥ 60 years were associated poor prognosis. Multivariate analysis indicated that for all tumours, males and females, high BCL2 expression was associated with good prognosis. Further, independent of BCL2, age ≥ 60 years is an unfavourable prognostic factor. Conclusion: Expression of BCL2 may serve to distinguish prognosis within the individual clinicopathological categories. BCL2 is also an independent variable in all tumours, males and females, with high expression being associated with good prognosis.     

What is the value of hemoglobin as a prognostic and predictive factor in cancer?

Anemia is a frequently encountered complication in cancer, and is associated with fatigue and reduced quality of life. Retrospective analyses of data from patients with hematological malignancies and solid tumors provide evidence that a low baseline hemoglobin (Hb) level is a prognostic factor for poor outcome. Moreover, in some situations, low Hb is a negative predictive parameter in chemotherapy. The adverse impact of anemia has been documented in patients with lymphomas and leukemias, as well as in those with non–small-cell lung cancer, ovarian cancer, cervical cancer, renal cell carcinoma, head and neck cancer and other solid tumors. Studies in animal models support the role of low Hb levels as a negative prognostic and predictive factor. Although prospective clinical trials are still needed to confirm that Hb levels affect outcome, the available evidence suggests that there is more than one reason to pay attention to Hb levels in cancer patients: increasing Hb not only corrects anemia and thereby improves physical functioning and quality of life, but also may improve clinical outcomes.     

Does biomolecular characterization of stage II/III colorectal cancer have any prognostic value?

As new improvements in the treatment of colorectal cancer have become available, it has become important to understand the benefits of new therapies or the deleterious effects stemming from the increased risk of toxicity. In particular, a more rational approach to adjuvant chemotherapy for patients with stage II/III disease should be defined by understanding which patients have a higher recurrence risk. Many studies have investigated several molecular markers, but none has been definitively associated with patient outcome. We present a review of studies that have evaluated the immunohistochemical correlation between expression of some biomarkers, such as thymidylate synthase, p53, Ki-67, Bcl-2, and microsatellite instability status expressed by Mut-L homologue 1 and Mut-S homologue 2 proteins, and the prognosis of patients with stage II/III colorectal cancer. We have evaluated studies in which > or = 100 patients were involved in an effort to ensure a representative study group. The only biomarker likely to have a prognostic value is microsatellite instability status, which correlated with a better prognosis.     

Why do results conflict regarding the prognostic value of the methylation status in colon cancers? the role of the preservation method

Background  

In colorectal carcinoma, extensive gene promoter hypermethylation is called the CpG island methylator phenotype (CIMP). Explaining why studies on CIMP and survival yield conflicting results is essential. Most experiments to measure DNA methylation rely on the sodium bisulfite conversion of unmethylated cytosines into uracils. No study has evaluated the performance of bisulfite conversion and methylation levels from matched cryo-preserved and Formalin-Fixed Paraffin Embedded (FFPE) samples using pyrosequencing.     

Does the degree of intratumoural microvessel density and VEGF expression have prognostic significance in osteosarcoma?

The role of angiogenesis as a prognostic indicator in cancer has been extensively studied in recent times with several studies demonstrating a positive correlation for various malignant tumours. However, the role of angiogenesis in osteosarcoma remains a topic of debate. In this study, we aim to evaluate the significance of intratumoural microvessel density (MVD) and the degree of vascular epithelial growth factor (VEGF) expression as markers of angiogenesis and correlate this with disease outcome. Archival paraffin-embedded pre-treatment biopsy tissue of patients treated at St. Vincent's Hospital, Melbourne, with non-metastatic osteosarcoma at initial diagnosis was reviewed. Tissue was processed for immunofluorescent staining of the microvascular endothelial cells with antibodies directed against CD31 and CD34. The degree of angiogenesis was assessed, as determined by the microvessel density (MVD). Further histological examination was performed to assess the degree of VEGF expression. Histological observations were correlated with various clinicopathological factors and patient outcome in terms of recurrence, metastasis and death. Twenty-five cases were reviewed, 15 were male and 10 were female, and the median age was 26 years (range, 13-85). The mean follow-up was 21.5 months (range, 3-75 months). The median MVD was 43 microvessels/0.26 mm2 (range, 25-54) and 46 microvessels/0.26 mm2 (range, 30-58) for CD31 and CD34, respectively. Despite the moderate to high vascularity, there was no significant difference noted between the MVD and disease outcome factors for both CD31 and CD34. There was a trend towards a higher MVD in patients aged > 40 years compared to those < 40 years (p = 0.110 for CD31 and p = 0.097 for CD34). In terms of VEGF expression, 24 of 25 cases demonstrated either moderate or strong expression; however, no prognostic significance was determined. In this study, we were able to demonstrate that osteosarcoma is a relatively vascular tumour; however, the degree of MVD and VEGF expression does not provide prognostic information. It is likely that angiogenesis plays a key role in the pathogenesis of osteosarcoma and is, therefore, a potential target for novel anti-angiogenic therapies.     

The Simpson grading in meningioma surgery: does the tumor location influence the prognostic value?

Journal of Neuro-Oncology - In meningiomas, location-specific differences of the prognostic value of the Simpson classification are sparsely investigated but can influence strategy of surgery. We...     

Biomarker‐based diagnostic work‐up of invasive pulmonary aspergillosis in immunocompromised paediatric patients – is Aspergillus PCR appropriate?

Invasive aspergillosis (IA) is an important cause of morbidity and mortality in children and adults with haematologic malignancies or undergoing allogeneic haematopoietic stem cell transplantation, and early diagnosis and adequate antifungal treatment improve outcome. However, important differences exist between children and adults regarding epidemiology, underlying disease, and comorbidities, and the value of diagnostic tools to detect IA may also differ between these patient populations. Imaging studies are important to detect IA early, but typical findings of IA in chest computed tomography of adults are not detected in the majority of children. Whereas the value of the serum marker galactomannan seems to be comparable in children and adults, data on the performance of beta‐d ‐glucan in children are too limited for firm conclusions. PCR‐based assays are a promising diagnostic approach to rapidly and reliably detect and identify Aspergillus species in various clinical samples. However, as the majority of data on PCR‐based approaches has been obtained in adult patients, the value of this method in paediatric patients has not been defined to date. The present review focuses on studies of PCR‐based methods to diagnose IA in immunocompromised paediatric patients.     

Does combination of lipid formulation of amphotericin B and echinocandins improve outcome of invasive aspergillosis in hematological malignancy patients?

BACKGROUND:

In vitro and in vivo studies suggested that combination of lipid formulation of amphotericin B (L‐AMB) and echinocandins may have a synergistic or additive effect against Aspergillus. Furthermore, clinical studies suggested that this combination may improve response of invasive aspergillosis (IA).

METHODS:

Between August 1993 and June 2008, the authors identified a total of 159 patients with hematological malignancies who received salvage therapy for IA, with L‐AMB alone, echinocandins alone, or a combination of L‐AMB and echinocandins. Clinical characteristics, response to salvage therapy, and death up to 12 weeks after initiation of salvage therapy were retrospectively determined for all patients.

RESULTS:

Seventy patients received salvage therapy with L‐AMB, 18 patients received echinocandins alone (89% of whom received caspofungin), and 71 patients received the combination therapy of amphotericin B and echinocandins (90% of who received caspofungin). The 3 salvage treatment groups were comparable in regard to clinical characteristics; graft versus host disease was more frequently encountered in the echinocandin group, whereas more patients in the L‐AMB and combination groups had neutropenia and received immunotherapy. The response to salvage therapy was better in the echinocandin group (9% L‐AMB, 28% echinocandins, and 21% for combination therapy). The 3 groups had a comparable rate of Aspergillus‐related death (58%‐64%) and overall mortality (61%‐67%).

CONCLUSIONS:

The combination of L‐AMB and echinocandins offered no advantage in terms of improving response or reducing mortality over either drug alone. Hence, this combination will only add to the cost of therapy without any improvement in outcome in patients with hematological malignancies. Cancer 2010. © 2010 American Cancer Society.     

Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?

BACKGROUND: There are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor-free axillary lymph nodes on disease-free survival (DFS) in two distinct patient populations. METHODS: Eight hundred thirty-three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast-conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1-3 lymph nodes examined, Group 2 had 4-9 lymph nodes examined, Group 3 had 10-20 lymph nodes examined, and Group 4 had >20 lymph nodes examined. RESULTS: In the mastectomy cohort, with a median follow-up of 153 months, the 10-year DFS rate was 70%, 65%, 79%, and 81% for Groups 1-4, respectively. On multivariate analysis, pathologic tumor size (P<0.001) and the number of lymph nodes examined (P=0.010) were significant predictors for long-term DFS. In the breast-conservation cohort, with a median follow-up of 53 months, the 5-year DFS rate was 90%, 91%, 92%, and 95% for Groups 1-4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P=0.003) and tumor size (P=0.035). CONCLUSIONS: The recovery of <10 lymph nodes in lymph node-negative patients who underwent mastectomy resulted in a 10-15% decreased long-term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast-conservation therapy, which included radiation.     

The prognostic and potentially predictive value of the Laurén classification in oesophageal adenocarcinoma

AimTo investigate the histological subtypes of oesophageal adenocarcinoma according to the Laurén classification (intestinal/diffuse/mixed) in relation to tumour response to neoadjuvant treatment, and in relation to patients' survival after potentially curative treatment.MethodsData were collected from all oesophageal adenocarcinoma patients who underwent potentially curative treatment in our institute between 1998 and 2014. Treatment consisted of neoadjuvant chemoradiotherapy (36–50 Gy) followed by an oesophagectomy or definitive chemoradiotherapy (50–50.4 Gy). Clinical data were collected from patient records. All endoscopic biopsies and surgical resection specimens were reassessed to determine the histological subtype (intestinal, diffuse or mixed) and the Mandard tumour regression grade (TRG). The impact of the histological subtypes on survival was determined using a Cox model.ResultsMedian follow-up was 68 months. Diffuse and mixed type cancers accounted for 25% of oesophageal adenocarcinomas. Median overall survival differed significantly between patients with intestinal (n = 121, 39 months), diffuse (n = 28, 18 months) or mixed type (n = 11, 25 months) carcinomas (log rank, p = 0.023). In multivariable analysis, the diffuse type was associated with shorter survival (diffuse versus intestinal: hazard ratios 2.06, p = 0.006). A pathologically (near) complete response (TRG 1 or 2) was seen less frequently in diffuse type than in intestinal type carcinomas (24% versus 60%; p = 0.015).ConclusionsPatients with diffuse type oesophageal adenocarcinomas had a significantly worse prognosis than those with intestinal type carcinomas. Intestinal type carcinomas showed a better response to neoadjuvant chemoradiotherapy than diffuse type carcinomas. These differences call for the exploration of differentiated approaches in the potentially curative treatment of oesophageal adenocarcinomas.     

Treatment strategies for invasive aspergillosis in neutropenic patients: voriconazole or liposomal amphotericin-B?

The proportion of patients with cancers who develop invasive fungal infections has increased dramatically over the past few decades. Most of these infections are diagnosed in patients with hematological malignancies, mainly in patients with acute myeloid leukemia and those undergoing allogeneic hematopoietic stem cell transplantation. For years deoxycolate amphotericin B has been considered the drug of choice for the treatment of invasive aspergillosis, but it has been outclassed by its lipid formulations and new triazoles (i.e. voriconazole), that produced better response rates; nonetheless recovery from neutropenia remains the most important factor influencing outcome.     

Breast cancer in young women: have the prognostic implications of breast cancer subtypes changed over time?

We analyzed the impact of age according to subtype and compared outcomes for breast cancer (BC) patients across two time periods to determine whether the previously observed poor prognosis associated with BC in young women persists in the context of modern adjuvant therapies and relative to BC subtypes. Women aged <50 years (y) diagnosed with invasive BC between 1986–1992 and 2004–2007 were identified from British Columbia Cancer Agency’s Breast Cancer Outcomes Database and analyzed by age category (<40 and 40–49 years) and subtype. Subtypes were defined by immunohistochemistry. Relapse-free and overall survival (RFS and OS) were estimated using the Kaplan–Meier method. Multivariable analyses using Cox regression models were performed to adjust for prognostic variables. Age <40 was associated with inferior 5y-RFS for Luminal cases within both time cohorts (1986–1992: 65 vs. 77 %, P = 0.009, 2004–2007: 79 vs. 92 %, P = < 0.001). Inferior 5y-RFS was observed for those <40 with HER2-positive cancers in the 1986–1992, but not 2004–2007 cohort (49 vs. 66 %, P = 0.017, and 89 vs. 89 %, P = 0.879). No difference according to age was observed for triple-negative cancers in either time cohort (1986–1992: 60 vs. 63 %, P = 0.868, 2004–2007: 78 vs. 77 %, P = 0.933). 5y-RFS improved over time for all subgroups. OS for the Luminal subgroup improved for those 40–49 years but not <40 years. The effect of age varies with subtype. Age <40 years predicts inferior RFS and OS for Luminal BC in the modern era. Research efforts should target Luminal BC in young women for whom discrepancies in outcome persist.