The impact of renal cell carcinoma histopathological subtype on disease prognosis: A Canadian multi-institutional analysis.

480 Background: Renal cell carcinoma (RCC) is divided into several histopathological subtypes, each with significantly different clinical features. However, current data regarding the prognostic value of histological subtype is limited and conflicted. We examined the impact of RCC histology on disease prognosis in a large, multi-institutional Canadian analysis. Methods: The Canadian Kidney Cancer Information System (CKCis), a prospective database from 14 Canadian institutions, was utilized for the study. 1284 patients with non-metastatic RCC, who underwent surgical intervention with curative intent, were included in the study. Patients were stratified according to their primary histology and the Chi-squared test was used to determine associations between histopathology and clinical features. The impact of histology of disease-free survival (DFS) was determined with a multivariate analysis adjusted for age, gender, tumor size, tumor grade, and pathological stage. Results: Clear cell RCC was the most prevalent histological subtype found in 80.5% of patients. Histopathology was significantly associated with patient age, tumor grade, and pathological stage. Advanced stage disease (>T3) was associated with clear cell and papillary type II RCC (p<0.05). 90.7%, 86.7%, 78.5%, and 78.8% of patients with chromophobe, papillary type I, papillary type II, and clear cell RCC respectively, were free of disease after a median follow-up of 1.2 years. On multivariate analysis, histological subtype was a significant predictor of disease-free survival (DFS). When compared to clear cell histology, chromophobe RCC had a significantly higher DFS (HR=0.38, 95% CI 0.15-0.95, p<0.05), and papillary type I RCC had a trend towards a lower rate of disease progression (HR=0.31, 95% CI 0.08-1.28, p=0.05). Conclusions: This study demonstrates that histological subtype impacts disease progression. Histological subtype was independently associated with DFS in surgically treated RCC, specifically chromophobe RCC was shown to have the highest DFS. This may be used to help individualize patient treatment and follow-up based on primary tumor histology.

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Assessment of the treatment results in patients with breast cancer coexisting with pregnancy: A single-center observational study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e12566 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e12566-e12566

Author(s):

Anna Skrzypczyk-Ostaszewicz ◽

Agnieszka I. Jagiello-Gruszfeld ◽

Jerzy Giermek ◽

Zbigniew Nowecki

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Cancer Diagnosis ◽

Disease Free Survival ◽

Breast Cancer Diagnosis ◽

Diagnosis And Treatment ◽

Free Survival ◽

The Impact ◽

Disease Free

e12566 Background: This study discusses the analysis of the prospectively collected material on pregnant patients treated for breast cancer at the Department of Breast Cancer and Reconstructive Surgery of the Maria Skłodowska-Curie National Oncology Institute - National Research Institute (until 2020: Oncology Center - Institute) in Warsaw, in the years 1995 - 2020. 84 patients were included into the final analysis and 72 children were assessed simultaneously. Methods: The paper summarizes information on the diagnosis and treatment of breast cancer during pregnancy, the course of pregnancy and childbirth and the birth parameters of children i.e. weight, length and Apgar score, as well as the dependencies between them, mainly the impact of some breast cancer, diagnosis and treatment process features on the newborns. The patietnt’s survavial - DFS ( disease free survival) and OS ( overall survival) - was also analyzed. The course of breast cancer diagnosis and treatment data were obtained from the patients’ medical documentation (medical records) and from information provided by the mothers during follow-up visits and read in the children's health books. In order to answer the research questions, statistical analyzes were conducted using the IBM SPSS Statistics 26 package. Results: In the analyzed period, the disease recurrence was recognized in 34 (40.5%) patients, and 24 (28.6%) patients died. The median disease-free survival (DFS) was 12.3 years (147.5 months), and the median overall survival (OS) was not reached during the follow-up period. The estimated 5-year survival rates for DFS and OS were 57.9% and 74.5% respectively, and for 10-year survival - 51.4% and 64.5%. The study showed a statistically significant relationship between the baseline clinical advancement and DFS. It has been also analyzed how the diagnosis, treatment and method of pregnancy termination changed in two time periods (1995-2012 and 2013-2020). There were no statistically significant differences in survival - both DFS and OS - between the group of patients treated before and after 2012. In the assessment of the impact of some factors on the birth children parameters (weight and length), statistically significant results were obtained for: pregnancy advancement at diagnosis, breast cancer stage at diagnosis, pregnancy advancement at the start of chemotherapy, the chemotherapy regimen (classic or dose-dense), the number of cycles of chemotherapy given during pregnancy, and the number of drugs used in supportive treatment. Conclusions: The entire analysis has become not only an insightful characteristic of the studied group, but also these results may be important in everyday clinical practice and may help to optimize the management of an extremely complex and difficult situation, which is the coexistence of pregnancy with a malignant disease that threatens the mother’s life.

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BiovaxID™ Vaccine Therapy of Follicular Lymphoma in First Remission: Long-Term Follow-Up of a Phase II Trial and Status of a Controlled, Randomized Phase III Trial.

Blood ◽

10.1182/blood.v106.11.2441.2441 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2441-2441 ◽

Cited By ~ 8

Author(s):

Carlos Santos ◽

Lee Stern ◽

Laura Katz ◽

Thelma Watson ◽

Gause Barry

Keyword(s):

Clinical Trial ◽

Phase Ii ◽

Disease Free Survival ◽

T Cell Response ◽

Phase Iii ◽

Patient Specific ◽

Free Survival ◽

The Impact ◽

Disease Free

Abstract Malignant B-cells in Follicular Non-Hodgkin’s Lymphoma expresses a clonal idiotype immunoglobulin which can serve as the basis for a patient-specific anti-idiotype vaccine. In a previous single-arm Phase II study by Bendandi, et al (Nature Med5:1171–1177, 1999), we evaluated the ability of tumor-specific idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) administered concurrently with granulocyte-monocyte colony-stimulating factor (GM-CSF) adjuvant to induce complete remissions and molecular remissions in treated patients. The vaccine formulation induced a tumor-specific cytotoxic CD8+ and CD4+ T-cell response in patients in first complete remission after standard chemotherapy, as well as achieved molecular remissions in 8 of 11 of these patients. Data available at the time of this abstract for the 20-patient cohort, indicates a median follow-up of 9.167 years. 9 patients (45 %) remain in continuous first CR at their most recent follow-up (either in 2004 or 2005), and overall survival is 95%. The data further indicates the median disease free survival for the cohort is 96.5 months (8.04 years). To date there have been no additional reported mortalities in this cohort. As of August 2005, we report the progress of the Phase III clinical trial for this vaccine, opened in January 2000 by the NCI to evaluate the impact of this hybridoma-based Id vaccine on disease-free survival in a group of up to 375 previously untreated patients who have attained a CR or CRu from PACE [Prednisone, Doxorubicin, Cyclophosphamide, and Etoposide (ProMACE without methotrexate)] chemotherapy, and who are randomized to receive either vaccine or control. To date, 187 patients have been accrued onto the study. Of those patients, 145 (77.5%) achieved a CR or Cru and are being followed in this ongoing clinical trial.

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Allogeneic Transplantation for Adult Acute Lymphoblastic Leukemia (ALL) with Rituximab or Campath I-H.

Blood ◽

10.1182/blood.v104.11.5132.5132 ◽

2004 ◽

Vol 104 (11) ◽

pp. 5132-5132

Author(s):

Issa F. Khouri ◽

Rima M. Saliba ◽

Partow Kebriaei ◽

Carrie Ma ◽

Cindy Ippoliti ◽

...

Keyword(s):

Median Time ◽

Acute Gvhd ◽

Disease Free Survival ◽

Disease Status ◽

Allogeneic Transplantation ◽

Study Group ◽

Free Survival ◽

The Impact ◽

Disease Free

Abstract Because of potential synergy with chemotherapy and non-overlapping toxicity, we investigated the addition of Rituximab or Campath 1-H to the standard myeloablative conditioning regimen of cyclophosphamide (60 mg/kg daily x 2) and total body irradiation (12.0 Gy in four fractions) prior to allogeneic transplantation for ALL. Transplantation was performed on day 0. Rituximab was added if patients’ disease expressed CD20+ > 20% by flow-cytometry. It was administered (375 mg/m2 ) on days −6, −1, +7 and +14. Campath I-H (10 mg daily intravenously, days −6 to −2) was added if patients’ CD20 expression was <20% and CD52 >20%. Thirty-two adult consecutive patients were studied. Eleven were in first remission with poor prognostic features, 11 in 2nd remission, and 10 were ≥ 3rd remission, or in relapse. Twenty-nine patients had B-cell, two had T-cell and one had an undifferentiated phenotyping. The study group included 19 males and 13 females of median age 35 yrs (range, 19–57). Median # of prior chemoregimens received was 2 (range, 1–6). In both groups of patients, prophylaxis for GVHD consisted of a combination of tacrolimus and methotrexate. Pharmacokinetic studies in patients who received Campath I-H showed no detectable level of the antibody one-day prior to- or after the infusion of the donor graft. Median follow-up for survivors was 19 months. Outcomes were: Campath-study group Rituximab-study group P -value Prior Chemoregimens (range) 2(1–6) 2(1–3) 0.04 Donor Type Matched unrelated 3(28%) 8(38%) 0.2 Matched sibling 7(63%) 12(57%) Mismatched sibling 1(9%) 1(5%) Cell Source PB 8(73%) 11(52%) 0.2 Marrow 3(27%) 10(48%) Disease Status CR1/CR2 5(45%) 17(81%) 0.05 Others 6(55%) 4(19%) Median time ANC >500 13 12 0.07 (range) (11–17) (10–24) Median time Platelets >20K 13 13 0.8 (range) (6 – 31) (7 – 34) Day 100 TRM 0 1(5%) Acute GVHD II–IV (N,% kM) 2 (18%) 5 (24%) 0.7 Acute GVHD III–IV (N, % kM) 0 2 (9%) Chronic extensive GVHD (N, cumulative incidence) 3 (27%) 9 (54%) 0.4 Overall Survival (18 mos) (95% CI) 53% (21 – 77) 52% (26 – 73) 0.9 Disease-free survival (18 mos) (95% CI) 54% (23 – 75) 37% (15 – 60) 0.8 No prognostic factor was found to be of significance for survival, disease-free survival, or relapse. This included: age (<35 vs ≥ 35), source of graft, disease status at transplant, # prior regimens (<2 vs ≥ 2), acute or chronic GVHD, use of Rituximab or Campath. Our results indicate that the addition of Rituximab or Campath I-H in allogeneic transplantation for ALL is safe. There was no delay in engraftment and no added toxicity or risk of mortality. Longer follow-up is needed to evaluate the impact of this strategy upon survival and relapse.

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Adherence to breast cancer guidelines is associated with better survival outcomes: a systematic review and meta-analysis of observational studies in EU countries

BMC Health Services Research ◽

10.1186/s12913-020-05753-x ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Ignacio Ricci-Cabello ◽

Adrián Vásquez-Mejía ◽

Carlos Canelo-Aybar ◽

Ena Niño de Guzman ◽

Javier Pérez-Bracchiglione ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Health Outcomes ◽

Guideline Adherence ◽

Disease Free Survival ◽

Risk Of Bias ◽

Free Survival ◽

The Impact ◽

Disease Free

Abstract Background Breast cancer (BC) clinical guidelines offer evidence-based recommendations to improve quality of healthcare for patients with or at risk of BC. Suboptimal adherence to recommendations has the potential to negatively affect population health. However, no study has systematically reviewed the impact of BC guideline adherence -as prognosis factor- on BC healthcare processes and health outcomes. The objectives are to analyse the impact of guideline adherence on health outcomes and on healthcare costs. Methods We searched systematic reviews and primary studies in MEDLINE and Embase, conducted in European Union (EU) countries (inception to May 2019). Eligibility assessment, data extraction, and risk of bias assessment were conducted by one author and crosschecked by a second. We used random-effects meta-analyses to examine the impact of guideline adherence on overall survival and disease-free survival, and assessed certainty of evidence using GRADE. Results We included 21 primary studies. Most were published during the last decade (90%), followed a retrospective cohort design (86%), focused on treatment guideline adherence (95%), and were at low (80%) or moderate (20%) risk of bias. Nineteen studies (95%) examined the impact of guideline adherence on health outcomes, while two (10%) on healthcare cost. Adherence to guidelines was associated with increased overall survival (HR = 0.67, 95%CI 0.59–0.76) and disease-free survival (HR = 0.35, 95%CI 0.15–0.82), representing 138 more survivors (96 more to 178 more) and 336 patients free of recurrence (73 more to 491 more) for every 1000 women receiving adherent CG treatment compared to those receiving non-adherent treatment at 5 years follow-up (moderate certainty). Adherence to treatment guidelines was associated with higher costs, but adherence to follow-up guidelines was associated with lower costs (low certainty). Conclusions Our review of EU studies suggests that there is moderate certainty that adherence to BC guidelines is associated with an improved survival. BC guidelines should be rigorously implemented in the clinical setting. Trial registration PROSPERO (CRD42018092884).

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Predictors of survival in non-metastatic renal cell cancer after surgery: A retrospective analysis

Journal of Onco-Nephrology ◽

10.1177/2399369319842293 ◽

2019 ◽

Vol 3 (2) ◽

pp. 70-79

Author(s):

Ines Zemni ◽

Houyem Mansouri ◽

Sabrine Haddad ◽

Mohamed Ali Ayadi ◽

Maher slimene ◽

...

Keyword(s):

Renal Cell ◽

Renal Carcinoma ◽

Clear Cell ◽

Cell Cancer ◽

Disease Free Survival ◽

Fuhrman Grade ◽

Free Survival ◽

Cell Renal Carcinoma ◽

Disease Free

Aim: To investigate the prognostic significance of clinical and pathological factors of non-metastatic renal cell cancer after surgery. Patients and methods: We conducted a retrospective cohort study based on the records of patients with non-metastatic renal cancer submitted to radical or partial nephrectomy between 2000 and 2015 in Salah-Azaiez Institute. Results: Median follow-up was 38 months (interquartile range: 20–64). Five-year overall and disease-free survival were 53.8% and 43.1%. In the multivariate setting, lymph node invasion (p = 0.01), clear cell renal carcinoma subtype (p = 0.014), and tumor necrosis (p = 0.009) were the only independent statistically significant predictors of disease-free survival, while Fuhrman grade (p = 0.025), clear cell renal carcinoma subtype (p = 0.044), and TNM stage (0.041) were the only factors correlated with overall survival. Conclusion: For patients with non-metastatic renal cell carcinoma, independent predictors of disease-free survival and overall survival were clear cell renal cell carcinoma, Fuhrman grade, TNM stage, lymph node invasion, and tumor necrosis. Such information could be used to guide the intensity of follow-up and identify high-risk patients who can be targeted for adjuvant therapy trials.

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The pattern of prostate cancer local recurrence after radiation and salvage cryoablation

Canadian Urological Association Journal ◽

10.5489/cuaj.748 ◽

2013 ◽

Vol 5 (6) ◽

pp. 125 ◽

Cited By ~ 4

Author(s):

Chee Kwan Ng ◽

Naji J. Touma ◽

Venu Chalasani ◽

Madeleine Moussa ◽

Donal B. Downey ◽

...

Keyword(s):

Local Recurrence ◽

Prognostic Value ◽

Cox Regression ◽

Disease Free Survival ◽

Free Survival ◽

Prostate Biopsies ◽

Before And After ◽

The Impact ◽

Disease Free

Objective: We assessed the pattern of local recurrence after salvagecryoablation of the prostate, and the impact of local recurrence onintermediate-term outcome.Methods: One hundred twenty-two patients who underwentsalvage cryoablation were studied after a mean follow-up of 56months. Serial prostate biopsy was carried out after cryoablation.The histopathology of prostate biopsies before and after cryoablationwere compared. The prognostic value of post-cryoablationbiopsy was assessed with the Cox regression method.Results: 23.1% of patients had a positive biopsy for prostate cancerfollowing salvage cryoablation. Most cancer recurrences occurredin the apex (51.5%), base (21.2%) and seminal vesicles (18.2%).The presence of cancer at the base of the prostate was found tobe a prognostic factor for eventual biochemical failure. Overall5-year biochemical disease-free survival (bDFS) was 28%, howeverpatients with cancer at the base of the prostate had a 5-yearbDFS of 0%.Conclusion: Cancer recurrences occurred in areas where aggressivefreezing was avoided as it might result in serious problems (e.g.,urethro-rectal fistula and incontinence). Post-cryoablation biopsiesand the location of persistent disease are of prognostic value.

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TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

Cell Death and Disease ◽

10.1038/s41419-021-03734-4 ◽

2021 ◽

Vol 12 (5) ◽

Author(s):

Sha Zhou ◽

Jianhong Peng ◽

Liuniu Xiao ◽

Caixia Zhou ◽

Yujing Fang ◽

...

Keyword(s):

Colorectal Cancer ◽

Disease Free Survival ◽

Free Survival ◽

Epigenetic Regulator ◽

Crc Management ◽

Disease Free ◽

Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

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Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.5.987 ◽

2000 ◽

Vol 18 (5) ◽

pp. 987-987 ◽

Cited By ~ 62

Author(s):

Howard S. Hochster ◽

Martin M. Oken ◽

Jane N. Winter ◽

Leo I. Gordon ◽

Bruce G. Raphael ◽

...

Keyword(s):

Phase Ii ◽

Bone Marrow Involvement ◽

Survival Rates ◽

Eastern Cooperative Oncology Group ◽

Disease Free Survival ◽

Low Grade ◽

Survival Times ◽

Free Survival ◽

Disease Free

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.

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Treatment of adult acute lymphoblastic leukemia with intensive cyclical chemotherapy: a follow-up report

Blood ◽

10.1182/blood.v78.11.2814.2814 ◽

1991 ◽

Vol 78 (11) ◽

pp. 2814-2822 ◽

Cited By ~ 121

Author(s):

CA Linker ◽

LJ Levitt ◽

M O'Donnell ◽

SJ Forman ◽

CA Ries

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Lymphoblastic Leukemia ◽

Disease Free Survival ◽

Remission Induction ◽

Cell Phenotype ◽

Free Survival ◽

Prognostic Features ◽

Adult Acute Lymphoblastic Leukemia ◽

Disease Free

Abstract We treated 109 patients with adult acute lymphoblastic leukemia (ALL) diagnosed by histochemical and immunologic techniques. Patients were excluded only for age greater than 50 years and Burkitt's leukemia. Treatment included a four-drug remission induction phase followed by alternating cycles of noncrossresistant chemotherapy and prolonged oral maintenance therapy. Eighty-eight percent of patients entered complete remission. With a median follow-up of 77 months (range, 48 to 111 months), 42% +/- 6% (SEM) of patients achieving remission are projected to remain disease-free at 5 years, and disease-free survival for all patients entered on study is 35% +/- 5%. Failure to achieve remission within the first 4 weeks of therapy and the presence of the Philadelphia chromosome are associated with a 100% risk of relapse. Remission patients with neither of these adverse features have a 48% +/- 6% probability of remaining in continuous remission for 5 years. Patients with T-cell phenotype have a favorable prognosis with 59% +/- 13% of patients achieving remission remaining disease-free compared with 31% +/- 7% of CALLA-positive patients. Intensive chemotherapy may produce prolonged disease-free survival in a sizable fraction of adults with ALL. Improved therapy is needed, especially for patients with adverse prognostic features.

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