Wait times in diagnostic evaluation and treatment for patients with stage III non-small cell lung cancer in British Columbia.

Objective: Non-small cell lung cancer (NSCLC) is associated with poor prognosis. Although this is mostly due to the aggressive natural history of the disease, the effect of treatment delays on patient outcomes is unclear. This study examines various time intervals in the diagnostic evaluation, staging, and treatment of patients with unresectable stage III NSCLC.

Serum amyloid A overrides Treg anergy via monocyte-dependent and Treg-intrinsic, SOCS3-associated pathways.

The acute phase protein serum amyloid A (SAA) has been well characterized as an indicator of inflammation. Nevertheless, its functions in pro versus anti-inflammatory processes remain obscure. Here we provide unexpected evidences that SAA induces the proliferation of the tolerogenic subset of regulatory T cells (T(reg)).

Ten-year locoregional recurrence risks in women with nodal micrometastatic breast cancer staged with axillary dissection.

Purpose: To compare the locoregional recurrence (LRR) rates in patients with nodal mirometastases (pNmic) with those in patients with node-negative (pN0) and macroscopic node-positive (pNmac) breast cancer; and to evaluate the LRR rates according to locoregional treatment of pNmic disease.

Methods And Materials: The subjects were 9,616 women diagnosed between 1989 and 1999 with Stage pT1-T2, pN0, pNmic, or pNmac, M0 breast cancer. All women had undergone axillary dissection.

True recurrence versus new primary: an analysis of ipsilateral breast tumor recurrences after breast-conserving therapy.

Purpose: Ipsilateral breast tumor recurrence (IBTR) can occur in 5-20% of women with early-stage breast cancer treated with breast-conserving therapy. Two entities of IBTR have been described: true recurrence (TR), suggested to be regrowth of disease at the tumor bed, and new primary (NP), distinct from the index lesion in histology and location. This study compared survival outcomes between two patient cohorts classified clinically as having either TR or NP.

Extreme-risk prostate adenocarcinoma presenting with prostate-specific antigen (PSA)>40 ng/ml: prognostic significance of the preradiation PSA nadir.

Purpose: To examine the impact of patient, disease, and treatment characteristics on survival outcomes in patients treated with neoadjuvant androgen deprivation therapy (ADT) and radical external-beam radiotherapy (RT) for clinically localized, extreme-risk prostate adenocarcinoma with a presenting prostate-specific antigen (PSA) concentration of >40 ng/ml.

Methods And Materials: A retrospective chart review was conducted of 64 patients treated at a single institution between 1991 and 2000 with ADT and RT for prostate cancer with a presenting PSA level of >40 ng/ml. The effects of patient age, tumor (presenting PSA level, Gleason score, and T stage), and treatment (total ADT duration and pre-RT PSA level) characteristics on rates of biochemical disease-free survival (bDFS), prostate cancer-specific survival (PCSS), and overall survival (OS) were examined.

Three-year outcomes of a Canadian multicenter study of accelerated partial breast irradiation using conformal radiation therapy.

Purpose: To report 3-year toxicity, cosmesis, and efficacy of a multicenter study of external beam, accelerated partial breast irradiation (APBI) for early-stage breast cancer.

Methods And Materials: Between March 2005 and August 2006, 127 women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study involving five Canadian cancer centers. Women meeting predefined dose constraints were treated with APBI using 3 to 5 photon beams, delivering 35 to 38.

Increased use of regional radiotherapy is associated with improved outcome in a population-based cohort of women with breast cancer with 1-3 positive nodes.

Purpose: To examine use of and outcomes from adjuvant locoregional radiotherapy (LRRT) after breast-conserving surgery (BCS) for women with breast cancer with 1-3 positive nodes (1-3N+) before and after the 1997 publication of randomised trial evidence of a survival advantage from post-mastectomy LRRT.

Methods: Data were analysed for 2768 women diagnosed between 1989 and 2005 and referred to the British Columbia Cancer Agency with newly diagnosed pT1-3 breast cancer with 1-3N+, treated with BCS and RT. LRRT use was analysed over time.

Effect of radiotherapy boost and hypofractionation on outcomes in ductal carcinoma in situ.

Background: Boost radiotherapy (RT) improves outcomes for patients with invasive breast cancer, but whether this is applicable to patients with pure ductal carcinoma in situ (DCIS) is unclear. This study examined outcomes from whole breast RT, with or without a boost, and the impact of different dose-fractionation schedules in a population-based cohort of women with pure DCIS treated with breast-conserving surgery (BCS).

Methods: Data was analyzed for 957 subjects diagnosed between 1985 and 1999.

Ipsilateral breast tumor recurrence after breast-conserving therapy.

In the modern era of breast-conserving therapy for early-stage breast cancer, ipsilateral breast tumor recurrence (IBTR) represents an increasingly common clinical dilemma. Two kinds of IBTRs have been described: true recurrences, which represent regrowth of uneradicated initial disease, and new primaries, which may be distinct from the index lesion in histology and location. Whether these two entities have different biologies and survival prognoses remains unclear.

Prospective evaluation of a 12-week walking exercise program and its effect on fatigue in prostate cancer patients undergoing radical external beam radiotherapy.

Objective: To evaluate tolerability and compliance to a walking exercise program and its effect on fatigue during and after radical external beam radiation therapy (EBRT) for prostate cancer.

Methods: A total of 50 subjects with prostate cancer undergoing EBRT over 6 to 8 weeks were prospectively accrued to an exercise intervention group, matched for age and clinical characteristics to 30 subjects in a historical control group who underwent EBRT with no specific exercise intervention. Starting 1 week before EBRT, exercise participants performed moderate-intensity walking targeting 60% to 70% age-predicted maximum heart rate, at least 20 min/d, 3 d/wk over 12 weeks.

Treatment outcomes of locally advanced oropharyngeal cancer: a comparison between combined modality radio-chemotherapy and two variants of single modality altered fractionation radiotherapy.

Purpose: To compare outcomes in patients with locally advanced oropharyngeal cancer treated with radio-chemotherapy (RT-CT), accelerated fractionation radiotherapy (AccRT), or hypofractionated radiotherapy (HypoRT).

Methods And Materials: Subjects were 321 consecutive patients with newly diagnosed oropharyngeal cancer, Stage III or IVA/B, treated between January 2001 and December 2005 at the BC Cancer Agency with RT-CT (n = 157), AccRT (n = 57), or HypoRT (n = 107). Outcomes examined were disease-specific survival (DSS), locoregional control (LRC), overall survival (OS), rate of G-tube use, and rate of hospitalization for acute complications.

Outcomes of node-negative breast cancer 5 centimeters and larger treated with and without postmastectomy radiotherapy.

Purpose: The role of adjuvant postmastectomy radiotherapy (PMRT) remains controversial for the rare presentation of pT3pN0cM0 breast cancer. The present analysis examined locoregional recurrence (LRR) and breast cancer-specific survival (BCSS) in pT2 = 5.0-cm and pT3 >5.

Predictors of local recurrence in a population-based cohort of women with ductal carcinoma in situ treated with breast conserving surgery alone.

Background: To identify prognostic indicators of local recurrence (LR) in patients with ductal carcinoma in situ (DCIS) of the breast treated with breast conserving surgery (BCS) alone.

Methods: A retrospective study was conducted of all women with pure DCIS, diagnosed 1985-1999, referred for tertiary oncologic opinion in British Columbia, treated with BCS without adjuvant radiotherapy. Kaplan-Meier local control (LC) and breast cancer specific survival (BCSS) estimates for the entire group were plotted.

I-Ag7 is subject to post-translational chaperoning by CLIP.

Several MHC class II alleles linked with autoimmune diseases form unusually low-stability complexes with class II-associated invariant chain peptides (CLIP), leading us to hypothesize that this is an important feature contributing to autoimmune pathogenesis. We recently demonstrated a novel post-endoplasmic reticulum (ER) chaperoning role of the CLIP peptides for the murine class II allele I-E(d). In the current study, we tested the generality of this CLIP chaperone function using a series of invariant chain (Ii) mutants designed to have varying CLIP affinity for I-A(g7).

Primary sarcoma of the mediastinum: a report of 16 cases referred to the British Columbia Cancer Agency.

Background: Sarcoma arising in the mediastinum is a rare entity. This study evaluates treatment and survival in a cohort of patients with primary mediastinal sarcoma.

Methods: Between 1990 and 2006, 16 patients were referred to the British Columbia Cancer Agency with histologically confirmed sarcoma of mediastinal origin.

DM influences the abundance of major histocompatibility complex class II alleles with low affinity for class II-associated invariant chain peptides via multiple mechanisms.

DM catalyses class II-associated invariant chain peptide (CLIP) release, edits the repertoire of peptides bound to major histocompatibility complex (MHC) class II molecules, affects class II structure, and thereby modulates binding of conformation-sensitive anti-class II antibodies. Here, we investigate the ability of DM to enhance the cell surface binding of monomorphic antibodies. We show that this enhancement reflects increases in cell surface class II expression and total cellular abundance, but notably these effects are selective for particular alleles.

Masking of a cathepsin G cleavage site in vivo contributes to the proteolytic resistance of major histocompatibility complex class II molecules.

The expression of major histocompatibility complex class II (MHC II) molecules is post-translationally regulated by endocytic protein turnover. Here, we identified the serine protease cathepsin G (CatG) as an MHC II-degrading protease by in vitro screening and examined its role in MHC II turnover in vivo. CatG, uniquely among endocytic proteases tested, initiated cleavage of detergent-solubilized native and recombinant soluble MHC II molecules.

Among women who experience a recurrence after postmastectomy radiation therapy irradiation is not associated with more aggressive local recurrence or reduced survival.

Recent pre-clinical models suggest that radiation can promote tumor aggressiveness. We hypothesized that if this were occurring clinically, locoregional recurrences (LRRs) after postmastectomy radiation therapy (PMRT) would lead to lower survival than LRR after mastectomy alone. This study used two independent datasets to compare survival after LRR in women treated with versus without PMRT.

Micrometastatic node-positive breast cancer: long-term outcomes and identification of high-risk subsets in a large population-based series.

Purpose: The prognostic implication of breast cancer with nodal micrometastases measuring >0.2 mm but < or =2 mm (pNmic) is unclear. This study evaluates survival in pNmic relative to node-negative (N0) and macroscopic node-positive (pNmac) disease in a large population-based series.

A low-dose ipsilateral lung restriction improves 3-d conformal planning for partial breast radiation therapy.

In trials of 3D conformal external beam partial breast radiotherapy (PBRT), the dosimetrist must balance the priorities of achieving high conformity to the target versus minimizing low-dose exposure to the normal structures. This study highlights the caveat that in the absence of a low-dose lung restriction, the use of relatively en-face fields may meet trial-defined requirements but expose the ipsilateral lung to unnecessary low-dose radiation. Adding a low-dose restriction that ≤ 20% of the ipsilateral lung should receive 10% of the prescribed dose resulted in successful plans in 88% of cases.

Validation of a web-based predictive nomogram for ipsilateral breast tumor recurrence after breast conserving therapy.

PURPOSE IBTR! version 1.0 is a web-based tool that uses literature-derived relative risk ratios for seven clinicopathologic variables to predict ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT). Preliminary testing demonstrated over-estimation in high-risk subgroups.

Prognostic value of nodal ratios in node-positive breast cancer: a compiled update.

The number of positive axillary nodes is a strong prognostic factor in breast cancer, but is affected by variability in nodal staging technique yielding varying numbers of excised nodes. The nodal ratio of positive to excised nodes is an alternative that could address this variability. Our 2006 review found that the nodal ratio consistently outperformed the number of positive nodes, providing strong arguments for the use of nodal ratios in breast cancer staging and management.

Population-based analysis of the frequency of anemia and its management before and during chemotherapy in patients with malignant lymphoma.

Objective: In patients with hematologic malignancies, chemotherapy can further suppress bone marrow production. Whereas measures to correct anemia can improve patients' function and quality of life, the intervention threshold and the methods of correcting anemia in patients with malignant lymphoma are not clear. This study evaluates the frequency of anemia and the interventions used to correct anemia before and during chemotherapy for patients with Hodgkin and non-Hodgkin lymphomas.

Does a three-field electron/minitangent photon technique offer dosimetric advantages to a multifield, photon-only technique for accelerated partial breast irradiation?

Purpose: To determine whether 3-field electron/minitangent photons (mixed-modality) technique improved dosimetry compared with a multifield, photon-only technique for accelerated partial breast irradiation (APBI).

Materials And Methods: Subjects were 20 breast cancer patients previously treated with photon-only APBI as part of a clinical trial to a dose of 38.5Gy/10 fractions in 5 days.

Treatment and outcomes in adult patients with primary cardiac sarcoma: the British Columbia Cancer Agency experience.

Background: To evaluate treatment and survival in a cohort of patients referred to a Canadian institution with newly diagnosed primary cardiac sarcoma.

Methods: Between 1990 and 2006, 16 patients were referred to the British Columbia Cancer Agency with pathologically confirmed sarcoma of cardiac origin. Retrospective chart review was performed to document patient, tumor, and treatment characteristics.