Marked improvements in survival of patients with rectal cancer in the Netherlands following changes in therapy, 1989–2006

BackgroundSince the 1990s, treatment of patients with rectal cancer has changed in the Netherlands. Aim of this study was to describe these changes in treatment over time and to evaluate their effects on survival.MethodsAll patients in the Netherlands Cancer Registry with invasive primary rectal cancer diagnosed during the period 1989–2006 were selected. The Cochran–Armitage trend test was used to analyse trends in treatment over time. Multivariate relative survival analyses were performed to estimate relative excess risk (RER) of dying.ResultsIn total, 40,888 patients were diagnosed with rectal cancer during the period 1989–2006. The proportion of patients with stages II and III disease receiving preoperative radiotherapy increased from 1% in the period 1989–1992 to 68% in the period 2004–2006 for younger patients (<75 years) and from 1% to 51% for older patients (?75 years), whereas the use of postoperative radiotherapy decreased. Administration of chemotherapy to patients with stage IV disease increased over time from 21% to 66% for patients younger than 75 years. Both males and females exhibited an increase in five-year relative survival from 53% to 60%. The highest increase in survival was found for patients with stage III disease. In the multivariate analyses survival improved over time for patients with stages II–IV disease. After adjustment for treatment variables, this improvement remained significant for patients with stages III and IV disease.ConclusionsThe changes in therapy for rectal cancer have led to a markedly increased survival. Patients with stage III disease experienced the greatest improvement in survival.     

Does histology influence prognosis in patients with early-stage cervical carcinoma?

BACKGROUND: The objective of this study was to examine the influence of histology on the outcome of patients with surgically treated, Stage IA-IB carcinoma of the uterine cervix. METHODS: All patient information was collected prospectively and was extracted subsequently from the University of Toronto cervical carcinoma surgery data base. Selection criteria for surgery were based on tumor size and were independent of histology. Patients with adenocarcinoma were separated into two groups: those with mucinous/endometrioid adenocarcinoma (M/E AC) and those with adenosquamous/clear cell adenocarcinoma (AS/CC AC). Statistical analysis used Wilcoxon rank tests, Mantel-Hanzel tests, chi-square tests, and Cox regression analyses. RESULTS: Between July 1984 and January 2000, 880 patients with Stage IA-IB cervical carcinoma underwent radical surgery, including pelvic lymphadenectomy, as the primary treatment. Two hundred fifty-five patients had M/E AC (29%), 81 patients had AS/CC AC (9%), and 544 patients had squamous cell carcinoma (SCC; 62%). Compared with patients who had SCC, patients with M/E AC had significantly more favorable prognostic characteristics: age (median, 39 years vs. 41 years; P < 0.03), depth of invasion (3.7 mm vs. 5.5 mm; P < 0.001), vascular space involvement (24% vs. 57%; P < 0.0001), Grade 2-3 tumor (40% vs. 78%; P < 0.0001), and pelvic lymph node metastases (4% vs. 8%; P < 0.04), respectively. Characteristics among patients with AS/CC AC tended have values similar to the median values for patients with SCC (or intermediate between the values for patients with M/E AC and the values for patients with SCC): age (38 years), depth of invasion (6 mm), vascular space involvement (40%), Grades 2-3 (70%), and pelvic lymph node metastases (6%). The 2-year and 5-year recurrence free survival rate was similar between patients with M/E AC and patients with SCC (95% vs. 94% and 90% vs. 90%, respectively); however, both were significantly superior to the rates for patients with AS/CC AC (2-year recurrence free survival rate: 86%, P < 0.03; 5-year recurrence free survival rate: 81%, P % 0.03). There were no differences in the pattern of first recurrence by histology. CONCLUSIONS: Patients with surgically treated Stage IA-IB cervical carcinoma with M/E AC and SCC histology have a similar prognosis. For patients with disease with AS/CC AC histology, the current results and the literature indicate that patients with uncommon histologies have an inferior recurrence free survival rate. Although the optimal therapy for these patients remains undefined, there is no obvious rationale for altering the treatment strategies from those currently employed for patients with M/E AC and SCC.     

Fulvestrant (Faslodex™): current status in the therapy of breast cancer

Fulvestrant (Faslodex?, formerly ICI 182,780) is a potent steroidal antiestrogen that mediates its effects by estrogen receptor downregulation. It appears to act as a pure anti-estrogen and exhibits none of the negative side effects associated with the partial agonist activity of tamoxifen. It has been shown to be as effective as the oral aromatase inhibitor anastrozole in postmenopausal women with advanced breast cancer who have progressed on prior endocrine therapy, principally tamoxifen. It therefore provides the clinician with an alternative therapeutic strategy following the development of tamoxifen resistance. Fulvestrant might also have potential as a follow-on therapy after tamoxifen in an adjuvant setting and help alleviate some of the concerns surrounding long-term (up to 5 years) tamoxifen therapy.     

Adjuvant therapy in patients with ductal carcinoma in situ of the breast: The Pandora’s box

Most patients with ductal carcinoma in situ of the breast (DCIS) are eligible for breast conservation treatment. The key management decision is whether to add radiotherapy and/or endocrine therapy to minimize the risk of a subsequent recurrence. Recent analyses indicating a lack of benefit in terms of breast cancer-associated mortality have suggested that more conservative approaches, omitting adjuvant therapy or even surgery, may be advisable in selected patients. These mortality observations are directly influenced by widespread use of mammographic screening which has opened a Pandora’s box of subclinical DCIS and early invasive lesions. Confusion as to how aggressively such possibly indolent lesions should be treated has led to misunderstandings among patients and medical professionals. While awaiting further prospective evidence from clinical trials, we endorse an active treatment of DCIS as the standard of care. Our rationale is twofold: invasive recurrences are associated with an increase in breast cancer mortality, which is not the only relevant endpoint for DCIS. The benefit of complete surgical excision, adjuvant radiotherapy and endocrine treatment in preventing recurrence and invasive progression has been demonstrated in DCIS. The challenge now is how to identify DCIS patients who will not progress to invasive carcinoma even without complete excision and, at the other extreme, those patients at the highest risk who require mastectomy for local control. The current controversies over whether and which adjuvant therapy should be implemented can at least in part be addressed by developing effective doctor-patient communications that enable mutual understanding about the management of this biologically heterogeneous disease.     

Is the International Federation of Gynecology and Obstetrics staging system for cervical carcinoma able to predict survival in patients with cervical carcinoma?: an assessment of clinimetric properties

BACKGROUND: The objective of this article was to assess the clinimetric properties of the International Federation of Gynecology and Obstetrics (FIGO) staging system of cervical carcinoma to determine whether it is an adequate prognostic tool for the survival of patients with cervical carcinoma. METHODS: The FIGO staging system for cervical carcinoma was evaluated with regard to item generation, item reduction, sensibility, reliability, and validity. RESULTS: Many statistically significant and clinically important variables have been omitted from the current staging system for cervical carcinoma. The item-reduction step for the formulation of the prognostic tool has not been described by the authors of the FIGO staging system, but a consensus process is assumed. There are no studies currently available to assess the reliability of interobserver and intraobserver variability in applying the staging system to patients with cervical carcinoma. A trial to assess the reliability of this tool is proposed by the authors. Although there are no prospective trials to assess the criterion validity of the FIGO staging system, there is enough literature to suggest that the staging system is not capable of discriminating with regard to patient survival within and between stages. CONCLUSIONS: The current FIGO staging system for cervical carcinoma does not fully meet the majority of methodologic criteria for a strong predictive tool. Developing an improved prognostic index containing a complete array of independently prognostic variables is suggested.     

Mineral water Volzhanka from Undorovskĭ spring in combined therapy of patients with nephrolithiasis and chronic pyelonephritis

Water loading is an essential component in therapy of nephrolithiasis, especially in the presence of small ureteral concrements or fragments after extracorporeal shock-wave lithotripsy. Saluretics, furosemide in particular, cause side effects. One of these is dyselectrolytemia due to potassium loss. Mineral waters have advantages in the treatment of nephrolithiasis and pyelonephritis as their drinking does not lead to electrolyte loss. Low mineral waters are highly diuretic, e.g. after drinking 1 liter of Volzhanka day-time diuresis increases by 300-400 ml. This relieves ureteral and calyceal-pelvic tonicity stimulating elimination of the concrements or their fragments after lithotripsy. Intake of Volzhanka proved effective in combined therapy of nephrolithiasis, calculous pyelonephritis, urate nephrolithiasis.     

The potential and feasibility of conservative therapy for the early stages of ovarian cancerĭ

Improvement in techniques of early diagnosis of ovarian cancer (OC) has highlighted the importance of development of methods of conservative surgery. Numerous researchers have failed so far to reach consensus on working out strategies of treatment. A retrospective analysis of clinico-morphological data on 176 patients with bordar-line and OC stage I (conservative surgery--46; radical--130) (1980-1985) showed that efficacy depended on tumor pattern rather than method of treatment. Given high risk of recurrence in unremoved ovary (2 out of 28 reproductive females), bilateral salpingo-oophorectomy without removal of the uterus is discussed as an alternative procedure of conservative therapy. Modern procedures of this therapy requiring accurate staging and monitoring can be carried out at large medical centers only.     

Does pretreatment HPV viral load correlate with prognosis in patients with early stage cervical carcinoma?

Objective

Recent data suggest that pretreatment HPV (Human papillomavirus) viral load is useful to predict the severity of intraepithelial lesions of the uterine cervix and formulate a treatment plan. However, the relationship between initial HPV viral load and prognosis of cervical cancer patients has not yet been clearly defined. The objective of this study was to determine whether HPV viral load has prognostic significance in patients with early stage cervical carcinoma treated by surgery.

Methods

A retrospective review of all patients with early stage cervical carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy at our institution from August 2003 to December 2007 was conducted. Patients were included only if they had pretreatment Hybrid Capture II test for HPV DNA detection.

Results

We identified 34 patients who met the inclusion criteria. Two groups were identified: patients who had low HPV viral load (≤100 RLU) versus those who had high viral load (>100 RLU). There were no differences in age, FIGO stage, histology, pathologic risk factors - tumor size, deep stromal invasion, lymph-vascular space invasion, parametrial extensions, vaginal margin involvement, and lymph node metastasis - and adjuvant CCRT. There was no significant difference of disease-free survival regard to pretreatment HPV viral load (p=0.7756).

Conclusion

In our study, survival was not significantly different between early stage cervical cancer patients who had low and high pretreatment HPV viral load. It seems that pretreatment HPV viral load may not be of help to predict disease prognosis.     

Multivariate analysis of clinicopathologic factors and the efficacy of postoperative IFN-γ adjuvant therapy in 115 patients with renal cell carcinoma

Background. In patients with renal cell carcinoma, the relationship between long term survival and clinicopathologic factors is not clear. We performed a retrospective analysis to determine the usefulness of clinicopathological factors as prognostic predictors in these patients and to evaluate the usefulness of interferon-gamma (IFN-γ) adjuvant therapy in their long term survival. Methods. We performed the analysis in 115 patients with renal cell carcinoma who underwent nephrectomy at our institution, between January 1980 and December 1997. Results. The median follow-up period was 40 months. The overall survival rates at 1, 5, and 10 years were 92.9%, 77.1%, and 77.1%, respectively. Four of the eight prognostic factors evaluated, including growth type, tumor size, clinical stage, local invasion (capsular invasion and microvascular invasion), histopathological architecture, and histopathological grade, were significant by the log-rank test. Multivariate analysis indicated that both growth type (P = 0.0005) and clinical stage (P = 0.0345) were significant independent prognostic factors. Among the 51 patients with clinical stage more advanced than Robson II, or with local invasion, the 5-year survival rate in those with IFN-γ treatment (n = 35) was 68.5 %, while the rate in those without 1FN-γ treatment (n = 16) was 48% (P = 0.0326). Conclusion. This analysis showed that tumor growth type and clinical stage were important prognostic factors. As no effective therapies have yet been established for advanced renal cell carcinoma, further investigation is warranted to determine the value of IFN-γ as a basic therapy for advanced renal cell carcinoma and for these carcinomas of the rapid-growth type. Received: April 10, 1998 / Accepted: January 14, 1999     

Does local recurrence affect the rate of distant metastases and survival in patients with early-stage breast carcinoma treated with breast-conserving therapy?

BACKGROUND: The purpose of the current analysis was to evaluate the impact of local recurrence (LR) on the development of distant metastases (DM), overall survival (OS), and cause specific survival (CSS) in patients with early-stage breast carcinoma who underwent conservative surgery (CS) and received postoperative radiotherapy (RT). METHODS: Between 1980 and 1995, 1169 patients underwent CS and received RT. All patients were followed for > 1 year and had < or = 4 lymph nodes involved with disease. The median duration of follow-up was 7.7 years. A Cox proportional hazards model was performed to evaluate the effect of LR on the development of DM and CSS. A matched-pair analysis that controlled for multiple prognostic factors also was performed comparing the outcomes of patients with and without LR. RESULTS: The LR rate was 11% at 12 years. For the entire population, LR led to poorer OS and CSS rates at 12 years compared with local control (LC) (71% vs. 81% [P = 0.001] and 69% vs. 88% [P < 0.001], respectively). In a Cox multiple regression model, LR was a significant predictor of disease specific mortality. The hazard ratio (HR) associated with LR was 2.69 for mortality and 2.67 for DM (P < 0.001 and P < 0.001, respectively). The median time from surgery to the development of DM was 3.8 years for patients without LR compared with 4.7 years for patients with LR. Patients who developed LR also had two peaks in the rate of DM (at 2.5 years and at 6.5 years) compared to only one peak (at 1.5 years) for patients who did not develop LR. The impact of LR on DM still was evident in patients with small tumors (< or = 2.0 cm; P < 0.001), negative lymph nodes (P = 0.004), or both (P < 0.001). Recurrent disease that developed outside of the surgical bed region had no negative effect on survival. In the matched-pair analysis (controlling for age, tumor size, grade, number of positive lymph nodes, and estrogen receptor status), LR remained the most significant predictor of mortality (HR: mortality, 5.86; DM, 6.43). CONCLUSIONS: The current results suggest that LR may be responsible for an increase in DM and disease specific mortality in patients who undergo CS and receive RT. This suggestion is reinforced by the distinct difference seen in the time distribution of DM after LR developed and by the fact that recurrent disease that originated outside of the surgical bed did not affect OS. These data reinforce the necessity to insure optimal LC in patients who are treated with breast-conserving therapy.     

Hemostatic changes after 1?month of thalidomide and dexamethasone therapy in patients with multiple myeloma

Thromboembolic events (TEE) are a serious clinical problem in multiple myeloma (MM) patients receiving thalidomide (T). Thirty-one MM patients were tested on diagnosis and after 2 and 4?weeks of therapy with T alone, or T in combination with dexamethasone (TD). Closure time (CT) in PFA-100 and P-selectin expression were assessed, as well as plasma levels of thrombin-antithrombin complexes (TAT), D-dimer (DD), soluble thrombomodulin (sTM) and von Willebrand factor antigen (vWF:Ag), along with the activity of coagulation factor VII and factor VIII. The concentration of vascular endothelial growth factor and its type 1 and 2 receptors were also assayed. On diagnosis, significantly prolonged median CT with both used cartridges, elevated P-selectin expression, DD concentration, TAT, vWF:Ag and factor VIII and factor VII activity were seen in the patient group as compared to controls. Therapy with these regimens caused marked shortening of CT with both cartridges. Treatment with TD leads to the significant increase in CD62P expression on platelets. Median TAT value increased significantly in relation to baseline after therapy with both regimens. Factor VIII activity exceeded 150?% in all patients after 2?weeks of TD therapy and was markedly elevated compared to baseline. One month of TD therapy significantly increased sTM concentration. These results demonstrate the enhanced platelet and coagulation system activation already present in MM patients on diagnosis, which is further increased by antimyeloma therapy. These changes are more pronounced after TD therapy and may promote TEE. Tested angiogenesis marker levels are elevated already on diagnosis, do not change after therapy and have no significant impact on the coagulation system in patients with MM.     

Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?

The objective of this study was to compare survival between all patients with radiographically resectable adenocarcinoma of the proximal pancreas who underwent preoperative chemoradiation therapy (PRE‐OP CRT) or surgical exploration first (SURGERY) with “intention to resect.” Pancreatic cancer patients who undergo resection after PREOP CRT live longer than patients who undergo resection without PREOP CRT, a difference that may be attributable to patient selection. We retrospectively identified 236 patients with pancreatic head adenocarcinoma seen between 1999 and 2007 with sufficient data to be confirmed medically and radiographically resectable. The outcomes of 144 patients who underwent PREOP CRT were compared to those of 92 patients who proceeded straight to SURGERY. The groups were similar in age and gender. Tumors were slightly larger in the PREOP CRT group (mean 2.5 cm vs. 2.1 cm, P < 0.01), and there were trends toward more venous abutment (54% vs. 39%, P = 0.06) and a higher Charlson comorbidity index (P = 0.1). In the PREOP CRT group, 76 patients (53%) underwent resection, 28 (19%) had metastatic and 17 (12%) locally unresectable disease after PREOP CRT, and 23 (16%) were not explored due to performance status or loss to follow‐up. In the SURGERY group, 68 patients (74%) underwent resection. Sixteen patients (17%) had metastatic and eight patients (9%) locally unresectable disease at exploration. In patients who underwent resection, the PREOP CRT group had smaller pathologic tumor size and lower incidence of positive lymph nodes than the SURGERY group but no difference in positive margins or need for vascular resection. Median overall survival (OS) in patients undergoing resection was 27 months in the PREOP CRT group and 17 months in the SURGERY group (P = 0.04). Median OS in all patients treated with PREOP CRT or surgically explored with intention to resect was 15 and 13 months, respectively, with superimposable survival curves. Despite a lower resection rate, the PREOP CRT group as a whole had a similar OS to the SURGERY group as a whole. For patients who underwent resection, those in the PREOP CRT had longer survival than those in the SURGERY group, suggesting that PREOP CRT allows better patient selection for resection. PREOP CRT should be considered an acceptable alternative for most patients with resectable pancreatic cancer. J. Surg. Oncol. 2012; 106:111–118. © 2012 Wiley Periodicals, Inc.     

Evaluation of the safety and efficacy of glucocorticoid therapy for hyperbilirubinemia in patients with hepatocellular carcinoma who have undergone transcatheter arterial chemoembolization

Objective The aim of this study was to analyze the safety and efficacy of glucocorticoid treatment for hyperbilirubinemia in patients with hepatocellular carcinoma(HCC)who have undergone transcatheter arterial chemoembolization(TACE).Methods We conducted a retrospective analysis of the clinical data of 198 patients with HCC who were admitted to The Fifth Medical Center of PLA General Hospital from June 2014 to August 2019 and underwent TACE therapy.The patients were divided into glucocorticoid(GCC)treatment group and control group.Standard liver-protecting procedures were used in both groups.The treatment group also received intravenous injections of methylprednisolone sodium succinate for 3–5 days.Reduction in bilirubin concentration,mean duration of hospitalization,and complications were compared between the two groups to investigate the safety and efficacy of GCCs for treatment of hyperbilirubinemia after TACE treatment.Results Bilirubin concentrations were significantly lower in the treatment group than in control group on days 3 and 5 after GCC/conventional liver-protecting treatment(P<0.05).The treatment group had significantly shorter durations of total post-surgery hospitalization,and recovery time than the control group(14.5±4.6 days vs.17.5±6.6 days,P<0.001;9.2±3.3 days vs.11.8±5.4 days,P=0.001;7.0±3.3 days vs.9.3±4.6 days,P<0.001).No GCC-associated complications were detected in the treatment group.Conclusion Short-term use of GCCs to treat hyperbilirubinemia in patients with HCC who have undergone TACE is safe and associated with rapid decline in bilirubin concentration and shorter hospital stay compared with patients who did not receive GCCs.     

Erythropoiesis-stimulating agents in the management of cancer patients with anemia： a meta-analysis

Background： Erythropoiesis-stimulating agents （ESAs） are widely used in the management of anemia in cancer patients. Despite their apparent effectiveness, recent studies have suggested that ESAs could result in serious adverse events and even higher mortality. The aim of the current study was to evaluate the benefits and risks of ESAs in the management of cancer patients with anemia using a recta-analysis. Methods： The initial literature search covered Medline, PubMed, Embase, and the Cochrane Center Register of Controlled Trials, and identified 1,569 articles. The final meta-analysis included eight randomized controlled trials （n=2,387） in cancer patients with 〈11 g/dL hemoglobin （Hb） at the baseline and target Hb （for stopping ESA treatment） at no more than 13 g/dL. The assessment measures included Hb response, blood transfusion rate and adverse events that included venous thromboemblism （VTE）, hypertension, and on-study mortality. The results are expressed as pooled odds ratio （OR）. Publication bias was assessed using funnel plot analysis. Results： ESAs significantly increased the Hb concentration [OR 7.85, 95% confidence interval （CI）： 5.85 to 10.53, P〈O.O01] and reduced the red blood cell （RBC） transfusion rate （OR 0.52, 95% CI： 0.42 to 0.65, P〈0.001）. ESAs did not increase the accumulated adverse events （OR 0.95, P=0.82）, or the on-study mortality （OR 1.09, P=0.47）. Conclusions： ESAs are not associated with increased frequency of severe adverse events in anemic cancer patients when the target Hb value is no more than 13 g/dL.     

Secular trends in the survival of patients with laryngeal carcinoma, 1995–2007

Background

Recent reports suggest a decline over time in the survival of patients newly diagnosed with laryngeal cancer in spite of developments in treatment practices. Our study set out to determine whether the survival of patients with laryngeal cancer in Ontario has changed over time.

Methods

This population-based cohort study of patients diagnosed with laryngeal cancer in the province of Ontario between 1995 and 2007 used data extracted from linked provincial administrative and registry databases. Its main outcomes were overall survival, laryngectomy-free survival, and survival ratio relative to an age- and sex-matched general population.

Results

The 4298 patients newly diagnosed with laryngeal cancer during the period of interest were predominantly men (n = 3615, 84.1%) with glottic cancer (n = 2787, 64.8%); mean age in the group was 66 years (interquartile range: 59–74 years). Patient demographics did not significantly change over time. Overall, 5-year survival was 57.4%; laryngectomy-free survival was 45.4%. Comparing patients from three eras (1995–1998, 1999–2003, 2004–2007) and adjusting for age, sex, and comorbidity status, we observed no differences in overall survival or laryngectomy-free survival over time. The 5-year relative survival ratio for patients with laryngeal cancer compared with an age- and sex-matched group from the general population was 81.1% for glottic cancer and 44.5% for supraglottic cancer.

Conclusions

In patients with a new diagnosis of laryngeal cancer, overall and laryngectomy-free survival have remained unchanged since the mid-1990s. New methods to improve survival and the rate of laryngeal preservation in this patient population are needed.