Reduced expression of members of the mhc-i antigen processing machinery in ethnic Uighur women with cervical cancer in the Xinjiang region of China

Objective

Cervical cancer is a major cause of mortality in Uighur women compared with Han women in the Xinjiang region of China. Although a reduction in the class i major histocompatibility complex (mhc-i) antigen processing machinery (apm) is associated with the development of cervical cancer, the mhc-i apm has not been studied in this particular group of women, who have the highest incidence rate of cervical cancer in China.

Study Design

We used immunohistochemical staining and polymerase chain reaction amplification of viral dna from infection with the human papilloma virus (hpv) to study the expression of members of the mhc-i apm in cervical cancer sections collected from Uighur and Han women and in cervicitis samples from age-matched counterparts.

Results

Expression of the molecules of interest was compared between two ethnic groups, and expression of transporter associated with antigen processing 1 and 2, heat shock protein 90, and calnexin were found to be reduced even more significantly in Han women with cervical cancer than in Uighur women with same disease. However, compared with Han women, Uighur women had a higher rate of infection with hpv 16.

Conclusions

The mhc-i apm were reduced in cervical cancer, with heterogeneity in the two ethnic groups. The reduction was more pronounced in Han women, who less frequently had hpv 16 infection, suggesting possible differences in the roles of members of the mhc-i apm and in the mechanisms of cervical cancer development in these two ethnic groups despite residence in the same region of China.     

Management of renal collecting duct carcinoma: a systematic review and the McMaster experience

Introduction

Collecting duct carcinoma (cdc) is a rare, aggressive form of renal carcinoma that presents at an advanced stage and has a poor prognosis. Little is known concerning the optimal management of cdc. We present the results of a systematic review addressing the management of cdc and the McMaster University cdc series.

Methods

The medline, Cochrane Library, and embase databases and conference proceedings were searched to identify studies relating to the management of cdc. Included studies reported on a minimum of 10 subjects receiving a single intervention. Series in which an evaluation of therapeutic effectiveness was not possible were excluded. The McMaster University (Hamilton, Ontario) series of 6 cases of cdc were retrospectively reviewed.

Results

We identified 3 studies relevant to the management of cdc that included a total of 72 patients. A gemcitabine–cisplatin or –carboplatin regimen resulted in a 26% objective response rate in 23 patients with metastatic cdc. Two additional studies indicated that 49 patients treated with immunotherapy achieved no response. In the McMaster series, cytoreductive nephrectomy was performed in 4 of 6 patients. In 2 patients, mvac therapy (methotrexate–vinblastine–doxorubicin–cisplatin) achieved no response. No significant therapeutic complications occurred, but survival was poor (median: 11 months; range: 10–33 months).

Conclusions

Our review and clinical experience suggest that the current standard of care for metastatic cdc is a gemcitabine–cisplatin regimen.     

Using proliferative markers and Oncotype DX in therapeutic decision-making for breast cancer: the B.C. experience

Background

Proliferative scoring of breast tumours can guide treatment recommendations, particularly for estrogen receptor (er)–positive, her2-negative, T1–2, N0 disease. Our objectives were to

• □ estimate the proportion of such patients for whom proliferative indices [mitotic count (mc), Ki-67 immunostain, and Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) recurrence score (rs)] were obtained.
• □ compare the indices preferred by oncologists with the indices available to them.
• □ correlate Nottingham grade (ng) and its subcomponents with Oncotype dx.
• □ assess interobserver variation.

Methods

All of the er-positive, her2-negative, T1–2, N0 breast cancers diagnosed from 2007 to 2011 (n = 5110) were linked to a dataset of all provincial breast cancers with a rs. A 5% random sample of the 5110 cancers was reviewed to estimate the proportion that had a mc, Ki-67 index, and rs. Correlation coefficients were calculated for the rs with ng subcomponent scores. Interobserver variation in histologic grading between outside and central review pathology reports was assessed using a weighted kappa test.

Results

During 2007–2011, most cancers were histologically graded and assigned a mc; few had a Ki-67 index or rs. The ng and mc were significantly positively correlated with rs. The level of agreement in histologic scoring between outside and central pathology reports was good or very good. Very few cases with a low mc had a high rs (1.8%).

Conclusions

Patients with low ng and mc scores are unlikely to have a high rs, and thus are less likely to benefit from chemotherapy. In the context of limited resources, that finding can guide clinicians about when a rs adds the most value.     

Serum C-reactive protein predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy

Background

We aimed to evaluate the association of serum C-reactive protein (crp) with prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.

Methods

We retrospectively reviewed 79 patients with locoregionally advanced nasopharyngeal carcinoma (cT3–4N0–3M0) treated with chemoradiotherapy. Chemoradiotherapy consisted of external-beam radiotherapy to the nasopharynx (70–80 Gy), the lymph node–positive area (60–70 Gy), and the lymph node–negative area (50–60 Gy) combined with 3 cycles of various platinum-based regimens delivered at 3-week intervals. Elevated crp was defined as more than 8 mg/L. The survival rate was calculated using the Kaplan–Meier method, and univariate and multivariate analyses (Cox proportional hazards model) were used to identify factors significantly associated with prognosis.

Results

During the median follow-up of 3.9 years (range: 1–5.5 years), 23 patients died from nasopharyngeal cancer. The 5-year cancer-specific survival (css) rate was 62.90%. Before chemoradiotherapy, 18 patients had high serum crp; the css rate in that subgroup was significantly worse than the rate in the remaining patients (p = 0.0002). Multivariate analysis showed that crp was an independent prognostic indicator of css, with a hazard ratio of 3.04 (95% confidence interval: 1.22 to 7.55; p = 0.017). Among the 18 patients with elevated serum crp, 9 achieved normal serum crp after chemoradiotherapy, of whom 5 remained living with no evidence of recurrence or metastasis during follow-up. By contrast, the remaining 9 patients in whom serum crp did not normalize after chemoradiotherapy died within 4.2 years.

Conclusions

Elevated serum crp before treatment predicts poor prognosis in patients with locoregionally advanced nasopharyngeal carcinoma treated with chemoradiotherapy.     

Comparing effectiveness with efficacy: outcomes of palliative chemotherapy for non-small-cell lung cancer in routine practice

Introduction

Randomized controlled trials (rcts) are the “gold standard” for establishing treatment efficacy; however, efficacy does not automatically translate to a comparable level of effectiveness in routine practice. Our objectives were to

• □ describe outcomes of palliative platinum-doublet chemotherapy (ppdc) in non-small-cell lung cancer (nsclc) in routine practice, in terms of survival and well-being; and
• □ compare the effectiveness of ppdc in routine practice with its efficacy in rcts.

Methods

Electronic treatment records were linked to the Ontario Cancer Registry to identify patients who underwent ppdc for nsclc at Ontario’s regional cancer centres between April 2008 and December 2011. At each visit to the cancer centre, a patient’s symptoms are recorded using the Edmonton Symptom Assessment System (esas). Score on the esas “well-being” item was used here as a proxy for quality of life (qol). Survival in the cohort was compared with survival in rcts, adjusting for differences in case mix. Changes in the esas score were measured 2 months after treatment start. The proportion of patients having improved or stable well-being was compared with the proportion having improved or stable qol in relevant rcts.

Results

We identified 906 patients with pre-ppdc esas records. Median survival was 31 weeks compared with 28–48 weeks in rcts. After accounting for deaths and cases lost to follow-up, we estimated that, at 2 months, 62% of the cohort had improved or stable well-being compared with 55%–63% who had improved or stable qol in rcts.

Conclusions

The effectiveness of ppdc for nsclc in routine practice in Ontario is consistent with its efficacy in rcts, both in terms of survival and improvement in well-being.     

Superficial parotid lobe–sparing delineation approach: a better method of dose optimization to protect the parotid gland in intensity-modulated radiotherapy for nasopharyngeal carcinoma

Purpose

We used a superficial parotid lobe–sparing delineation approach for dose optimization with better protection for the parotid glands in intensity-modulated radiotherapy (imrt) for nasopharyngeal carcinoma (npc) patients.

Methods

Compared with traditional contouring of the entire parotid glands as organs at risk (oars) in imrt for npc, we used a superficial parotid lobe–sparing delineation approach of contouring the superficial parotid lobes as oars. Changes in dose to the parotid glands, the targets, and other oars were evaluated.

Results

The mean dose to the parotid glands overall decreased by more than 4 Gy in the test plans. Impressively, the mean dose to the superficial parotid lobes in the test plans was not more than 30 Gy, regardless of clinical stage. In T1–3 npc patients, the dose distributions for targets were not significantly different in the control plans and the test plans. However, for some T4 patients, the dose distributions for targets and brainstem in the test plans could not meet clinical requirements.

Conclusions

The superficial parotid lobe–sparing delineation approach can significantly lower the mean dose to the entire parotid and to the superficial parotid lobe in T1–3 npc patients, which would be expected to result in less xerostomia and better quality of life for those patients.     

Panitumumab monotherapy compared with cetuximab and irinotecan combination therapy in patients with previously treated KRAS wild-type metastatic colorectal cancer

Background

The survival benefit for single-agent anti–epidermal growth factor receptor (egfr) therapy compared with combination therapy with irinotecan in KRAS wildtype (wt) metastatic colorectal cancer (mcrc) patients in the third-line treatment setting is not known. The objective of the present study was to describe the characteristics of, and to compare survival outcomes in, two cohorts of patients treated with either singleagent panitumumab or combination therapy with cetuximab and irinotecan.

Methods

The study enrolled patients with KRAS wt mcrc previously treated with both irinotecan and oxaliplatin who had received either panitumumab or combination cetuximab–irinotecan before April 1, 2011, at the BC Cancer Agency (bcca). Patients were excluded if they had received anti-egfr agents in earlier lines of therapy. Data were prospectively collected, except for performance status (ps), which was determined by chart review. Information about systemic therapy was extracted from the bcca Pharmacy Database.

Results

Of 178 eligible patients, 141 received panitumumab, and 37 received cetuximab–irinotecan. Compared with patients treated with cetuximab–irinotecan, panitumumab-treated patients were significantly older and more likely to have an Eastern Cooperative Oncology Group (ecog) ps of 2 or 3 (27.7% vs. 2.7%, p = 0.001). Other baseline prognostic variables and prior and subsequent therapies were similar. Median overall survival was 7.7 months for the panitumumab group and 8.3 months for the cetuximab–irinotecan group. Multivariate analysis demonstrated that survival outcomes were similar regardless of the therapy selected (hazard ratio: 1.28; p = 0.34). An ecog ps of 2 or 3 compared with 0 or 1 was the only significant prognostic factor in this treatment setting (hazard ratio: 3.37; p < 0.01).

Conclusions

Single-agent panitumumab and cetuximab–irinotecan are both reasonable third-line treatment options, with similar outcomes, for patients with chemoresistant mcrc.     

Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study

Background

Patients with cancer are often treated with glucocorticoids (gcs) as part of therapy, which may cause hyperglycemia. We sought to define the prevalence of, and risk factors for, hyperglycemia in this setting.

Methods

Adult patients taking gc as part of therapy protocols for primary brain tumour or metastasis, for lymphoma, or for bone marrow transplant (bmt) were screened with random glucometer measurements taken at least 3 hours after the last dose gcs.

Results

We screened 90 patients [44.4% women, 55.6% men; mean age: 59.6 years (range: 25–82 years); mean body mass index (bmi): 26.4 kg/m² (range: 15.8–45.3 kg/m²)] receiving gc as part of cancer treatment. Mean total daily gc dose in the group was 238.5 mg (range: 30–1067 mg) hydrocortisone equivalents. Hyperglycemia (glucose ≥ 8.0 mmol/L) was found in 58.9% (53 of 90), and diabetes mellitus (dm)–range hyperglycemia (glucose ≥ 11.1 mmol/L) in 18.9% (17 of 90). The mean time from gc ingestion to glucometer testing was 5.5 hours (range: 3–20 hours). Presence of hyperglycemia did not correlate with traditional dm risk factors such as age, sex, bmi, and personal or family history of dm. A longer interval from gc dose to testing (p < 0.05), a higher gc dose (p = 0.04), and a shorter interval between the preceding meal and testing (p = 0.02) were risk factors for hyperglycemia in some patient groups.

Conclusions

Glucocorticoid-induced hyperglycemia is common in patients undergoing cancer treatment and cannot be predicted by traditional risk factors for dm. We recommend that all cancer patients receiving gc be screened for hyperglycemia at least 4–6 hours after gc administration.     

Clinical analysis of osteosarcoma patients treated with high-dose methotrexate-free neoadjuvant chemotherapy

Objective

High-dose methotrexate (hdmtx) is a common therapeutic agent in the treatment of osteosarcoma. However, hdmtx is highly toxic and requires complex pharmacokinetic monitoring and leucovorin rescue. Thus, alternative therapeutic strategies are necessary. Here, we analyzed the clinical efficacy of a dia regimen (cisplatin–ifosfamide–doxorubicin) to evaluate its potential as an alternative to hdmtx–based therapy.

Methods

Patients received 12 cycles of chemotherapy administered over 2 years (2 preoperative cycles and 10 postoperative cycles). Cumulative dose was the same in all cycles: cisplatin 120 mg/m² on day 1 of week 1, followed by ifosfamide 2.0 g/m² days 1–5 of week 2, and doxorubicin 20 mg/m² days 1–3 of week 2.

Results

Between January 2004 and October 2008, 39 eligible patients (median age: 16 years) were enrolled, with 36 being evaluable for the study. Of those 36 patients, 20 (55.6%) had a good histologic response to preoperative chemotherapy (>90% tumour necrosis). The estimated 5-year rates of event-free survival (efs) and overall survival were 54.8% and 61.5% respectively.

Conclusions

The results of our study suggest that, in osteosarcoma patients, the dia regimen produces an efs rate and survival outcomes comparable to those attained with hdmtx–containing regimens, with fewer adverse reactions. The dia regimen is well tolerated, and we observed a high level of patient compliance. Our results demonstrate that hdmtx-free osteosarcoma treatment regimens can be effective, warranting further investigation.     

Economic evaluation of hormonal therapies for postmenopausal women with estrogen receptor–positive early breast cancer in Canada

Background

Aromatase inhibitor (ai) therapy has been subjected to numerous cost-effectiveness analyses. However, with most ais having reached the end of patent protection and with maturation of the clinical trials data, a re-analysis of ai cost-effectiveness and a consideration of ai use as part of sequential therapy is desirable. Our objective was to assess the cost-effectiveness of the 5-year upfront and sequential tamoxifen (tam) and ai hormonal strategies currently used for treating patients with estrogen receptor (er)–positive early breast cancer.

Methods

The cost-effectiveness analysis used a Markov model that took a Canadian health system perspective with a lifetime time horizon. The base case involved 65-year-old women with er-positive early breast cancer. Probabilistic sensitivity analyses were used to incorporate parameter uncertainties. An expected-value-of-perfect-information test was performed to identify future research directions. Outcomes were quality-adjusted life-years (qalys) and costs.

Results

The sequential tam–ai strategy was less costly than the other strategies, but less effective than upfront ai and more effective than upfront tam. Upfront ai was more effective and less costly than upfront tam because of less breast cancer recurrence and differences in adverse events. In an exploratory analysis that included a sequential ai–tam strategy, ai–tam dominated based on small numerical differences unlikely to be clinically significant; that strategy was thus not used in the base-case analysis.

Conclusions

In postmenopausal women with er-positive early breast cancer, strategies using ais appear to provide more benefit than strategies using tam alone. Among the ai-containing strategies, sequential strategies using tam and an ai appear to provide benefits similar to those provided by upfront ai, but at a lower cost.     

Prognostic factors associated with the response to sunitinib in patients with metastatic renal cell carcinoma

Objective

We investigated the prognostic clinicopathologic factors associated with overall survival (os) and progression-free survival (pfs) in the once-daily continuous administration of first-line sunitinib in a consecutive cohort of Turkish patients with metastatic renal cell carcinoma (rcc).

Methods

The study enrolled 77 Turkish patients with metastatic rcc who received sunitinib in a continuous once-daily dosing regimen between April 2006 and April 2011. Univariate analyses were performed using the log-rank test.

Results

Median follow-up was 18.5 months. In univariate analyses, poor pfs and os were associated with 4 of the 5 factors in the Memorial Sloan–Kettering Cancer Center (mskcc) score: Eastern Cooperative Oncology Group performance status of 2 or higher, low hemoglobin, high corrected serum calcium, and high lactate dehydrogenase. In addition to those factors, hypoalbuminemia, more than 2 metastatic sites, liver metastasis, non–clear cell histology, and the presence of sarcomatoid features on pathology were also associated with poor pfs; and male sex, hypoalbuminemia, prior radiotherapy, more than 2 metastatic sites, lung metastasis, nuclear grade of 3 or 4 for the primary tumour, and the presence of sarcomatoid features were also associated with poorer os. The application of the mskcc model distinctly separated the pfs and os curves (p < 0.001).

Conclusions

Our study identified prognostic factors for pfs and os with the use sunitinib as first-line metastatic rcc therapy and confirmed that the mskcc model still appears to be valid for predicting survival in metastatic rcc in the era of molecular targeted therapy.     

Adherence to and uptake of clinical practice guidelines: lessons learned from a clinical practice guideline on chemotherapy concomitant with radiotherapy in head-and-neck cancer

Background

Clinical practice guidelines (cpgs) are systematically developed statements designed to assist practitioners and patients in making decisions about appropriate heath care interventions. Clinical practice guidelines are expensive and time-consuming to create. A cpg on concurrent chemotherapy with radiation therapy (ccrt) was developed in Ontario at a time when treatment approaches for head-and-neck cancer were changing significantly.

Methods

An assessment of treatments and outcomes based on electronic and chart data obtained from a population-based study of 571 patients with oropharynx cancer treated in Ontario (2003–2004) was combined with a review of relevant knowledge transfer (publications and presentations at major meetings) to understand variation in adherence to a cpg.

Results

In 9 Ontario cancer treatment centres, ccrt was used for 55% of all patients with oropharyngeal cancer; however, at the centres individually, that proportion ranged from 82% to 39%. Furthermore, there was no agreement on the chemotherapy regimen: 2–4 years later (a period during which newer regimens were emerging), only 4 of 9 centres were following the guideline for most patients. When outcomes of treated patients were compared for centres with “higher” and “lower” use of ccrt, no difference in survival was observed (p = 0.64).

Conclusions

At a time of treatment evolution, the new guideline was controversial, and there are many reasons for the mixed adherence. An estimation of adherence should be included during both development and review of guidelines.     

Patient preferences for timing and access to radiation therapy

Purpose

Patient preferences for radiation therapy (rt) access were investigated.

Methods

Patients completing a course of rt at 6 centres received a 17-item survey that rated preferences for time of day; day of week; actual, ideal, and reasonable travel times for rt; and actual, ideal, and reasonable times between referral and first oncologic consultation. Patients receiving single-fraction rt or brachytherapy alone were excluded.

Results

Of the respondents who returned surveys (n = 1053), 54% were women, and 74% had received more than 15 rt fractions. With respect to appointment times, 88% agreed or strongly agreed that rt between 08h00 and 16h30 was preferred; 14%–15% preferred 07h30–08h00 or 16h30–17h00; 10% preferred 17h00–18h00; and 6% or fewer preferred times before 07h30 or after 18h00. A preference not to receive rt before 07h30 or after 18h00 was expressed by 30% or more of the respondents. When days of the week were considered, 18% and 11% would have preferred to receive rt on a Saturday or Sunday respectively; 52% and 55% would have preferred not to receive rt on those days. A travel time of 1 hour or less for rt was reported by 82%, but 61% felt that a travel time of 1 hour or more was reasonable. A first consultation within 2 weeks of referral was felt to be ideal or reasonable by 88% and 73% of patients respectively.

Conclusions

An rt service designed to meet patient preferences would make most capacity available between 08h00 and 16h30 on weekdays and provide 10%–20% of rt capacity on weekends and during 07h30–08h00 and 16h30–18h00 on weekdays. Approximately 80%, but not all, of the responding patients preferred a 2-week or shorter interval between referral and first oncologic consultation.     

After radiotherapy,do bone metastases from gastrointestinal cancers show response rates similar to those of bone metastases from other primary cancers?

Purpose

Reports investigating whether the response rates to palliative radiation therapy (rt) for painful bone metastases from gastrointestinal (gi) cancers are similar to rates for bone metastases from other primary cancer sites have been limited. The present study evaluated response rates for symptomatic bone metastases from gi cancers after palliative outpatient rt in the Rapid Response Radiotherapy Program (rrrp).

Patients and Methods

We identified 69 patients with bone metastases from gi primaries who received palliative rt in the rrrp clinic during 1999–2006. We extracted records for 31 of these patients during 1999–2003 from an rrrp database that used the Edmonton Symptom Assessment Scale (esas). Record for the remaining 38 patients during 2003–2006 were extracted from an rrrp database that used the Brief Pain Inventory (bpi). Eligibility criteria for encryption in the two rrrp databases and for collection of patient demographic information (age, sex, primary cancer site, and Karnofsky performance status) were identical.Response rates for this cohort of metastatic gi patients were then compared to rates for 479 patients receiving palliative rt for bone metastases from other primary cancer sites. Pain scores from the esas and bpi and data on analgesic consumption were collected at baseline and by telephone follow-up at 4, 8, and 12 weeks after rt for all patients. Complete (cr), partial (pr), and overall (cr+pr) responses were evaluated according to International Consensus Endpoints.

Results

Assessment of the 69 patients with metastatic gi cancers revealed cr, pr, and cr+pr rates of 18%, 42%, and 61% at 4 weeks; 22%, 35%, and 57% at 8 weeks; and 50%, 21%, and 71% at 12 weeks for evaluable patients. The 479 evaluable patients with metastatic cancer from other primary cancer sites had cr, pr, and cr+pr rates of 25%, 27%, and 51% at 4 weeks; 26%, 22%, and 48% at 8 weeks; and 22%, 29%, and 51% at 12 weeks. No statistically significant differences were observed in rt response rates for bone metastases from gi cancers than from other primary cancer sites.

Conclusions

After palliative rt, bone metastases from gi cancers demonstrate response rates that are similar to rates for metastases from other primary cancer sites. Patients with symptomatic bone metastases from gi malignancies should be referred for palliative rt as readily as patients with osseous metastases from other primary cancer sites.     

Irradiation after surgery for breast cancer patients with primary tumours and one to three positive axillary lymph nodes: yes or no?

Objective and Methods

We retrospectively analyzed clinicopathologic features and survival in breast cancer patients who had T1 or T2 primary tumours and 1–3 histologically involved axillary lymph nodes and who were treated with modified radical mastectomy without adjuvant radiotherapy (rt). We also explored prognosis to find the high- and low-risk groups.

Results

From May 2001 to April 2005, 368 patients treated at Tianjin Tumor Hospital met the study criteria. The 5- and 8-year rates were 7.2% and 10.7% for locoregional recurrence (lrr), 85.1% and 77.7% for disease-free survival (dfs), and 92.8% and 89.3% for overall survival (os). Multivariate Cox regression analysis showed that age, tumour size, estrogen receptor (er) status, and lymphovascular invasion (lvi) were independent prognostic factors for lrr and dfs. Based on 4 patient-related factors that indicate poor prognosis (age < 40 years, tumour > 3 cm, er negativity, and lvi), the high-risk group (patients with 3 or 4 factors, accounting for 12.5% of the cohort) had 5- and 8-year rates of 24.3% and 36.9% for lrr, 57.2% and 39.2% for dfs, and 74.8% and 43.8% for os compared with 5.0% and 7.1% for lrr, 88.9% and 83.1% for dfs, 91.6% and 83.4% for os in the low-risk group (patients with 0–2 factors, accounting for 87.5% of the cohort; p < 0.001).

Conclusions

Our study identified several risk factors that correlated independently with a greater incidence of lrr and distant metastasis in patients with T1 and T2 breast cancer and 1–3 positive nodes. Patients with 0–2 risk factors may not be likely to benefit from post-mastectomy rt, but patients with 3–4 risk factors may need rt to optimize locoregional control and improve survival.     

Ondansetron rapidly dissolving film for the prophylactic treatment of radiation-induced nausea and vomiting—a pilot study

Introduction

The purpose of the present study was to investigate the efficacy of an ondansetron rapidly dissolving film (rdf) in the prophylaxis of radiation-induced nausea and vomiting (rinv). Rapidly dissolving film formulations facilitate drug delivery in circumstances in which swallowing the medication might be difficult for the patient.

Methods

Patients undergoing palliative radiotherapy at risk for rinv were prescribed ondansetron rdf 8 mg twice daily while on treatment and were asked to complete a nausea and vomiting–specific daily diary, the Functional Living Index–Emesis (flie), and the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire–C15 Palliative (qlq-C15-pal). Patients were categorized as receiving primary or secondary prophylaxis based on whether they had already experienced emetic episodes. “Overall control” was defined as a maximum increase of 2 episodes of nausea or vomiting from baseline. “Acute phase” was defined as the days during radiation until the first day after radiation; “delayed phase” was defined as days 2–10 after radiation.

Results

The study accrued 30 patients. Rates of overall control for nausea and for vomiting during the acute phase in the primary prophylaxis group were 88% and 93% respectively; during the delayed phase, they were 73% and 75%. Rates of overall control for nausea and for vomiting during the acute phase in the secondary prophylaxis group were both 100%; during the delayed phase, they were 50%. The number of nausea and vomiting episodes was found to be significantly correlated with the flie and qlq-C15-pal questionnaires.

Conclusions

Ondansetron rdf is effective for the prophylaxis of rinv.     

Magnitude of change in alpha-fetoprotein in response to transarterial chemoembolization predicts survival in patients undergoing liver transplantation for hepatocellular carcinoma

Background

Downsizing strategies are often attempted for patients with hepatocellular carcinoma (hcc) before liver transplantation (lt). The objective of the present study was to determine clinical predictors of favourable survival outcomes after transarterial chemoembolization (tace) before lt for hcc outside the Milan criteria, so as to better select candidates for this strategy.

Methods

In this retrospective study, patients with hcc tumours either beyond Milan criteria (single lesion > 5 cm, 3 lesions with 1 or more > 3 cm) or at the upper limit of Milan criteria (single lesions between 4.1 cm and 5.0 cm), with a predicted waiting time of more than 3 months, received carboplatin-based tace treatments. Exclusion criteria for tace included Child–Pugh C cirrhosis or the presence of portal vein invasion or extrahepatic disease on imaging. Only patients without tumour progression after tace underwent lt.

Results

Of 160 hcc patients who received liver grafts between 1997 and 2010, 35 were treated with tace preoperatively. The median of the sum of tumour diameters was 6.7 cm (range: 4.8–8.5 cm), which decreased with tace to 5.0 cm (range: 3.3–7.0 cm) at transplantation (p < 0.0004). The percentage drop in alpha-fetoprotein (αfp) was a positive predictor (p = 0.0051) and the time from last tace treatment to transplantation was a negative predictor (p < 0.0001) for overall survival.

Conclusions

The percentage drop in αfp and a shorter time from the final tace treatment to transplantation significantly predicted improved overall survival after lt for hcc downsized with tace. As a serum marker, αfp should be followed when tace is used as a strategy to stabilize or downsize hcc lesions before lt.     

Incidence of taxane-induced pain and distress in patients receiving chemotherapy for early-stage breast cancer: a retrospective,outcomes-based survey

Introduction

With the widespread use of sequential anthracycline/taxane–based chemotherapy for early-stage breast cancer, clinicians are becoming rapidly aware of toxicities associated with those regimens. Despite the low incidence reported in the literature of significant arthralgia and myalgia with those regimens, it is clinically evident that a substantial proportion of patients develop such toxicities. We performed a pilot study to investigate the extent of this problem.

Patients and Methods

Patients who had received prior adjuvant or neoadjuvant chemotherapy [doxorubicin–cyclophosphamide followed by paclitaxel (ac-t), doxorubicin–cyclophosphamide followed by docetaxel (ac-d), or 5-fluourouracil–epirubicin–cyclophosphamide followed by docetaxel (fec-d)] completed a retrospective outcomes-based survey. The survey utilized the Functional Assessment of Cancer Therapy–Taxane Scale, the Memorial Symptom Assessment Scale, and a modified Brief Pain Inventory.

Results

Interviews were conducted with 82 patients. Interviewees had received ac-t (43%), fec-d (43%), and ac-d (14%). Pain as a side effect of either the anthracycline or the taxane chemotherapy was reported by 87% of patients. Most of the patients (79%) indicated that their worst pain occurred during the taxane component of treatment. Compared with paclitaxel, docetaxel was reported to cause more pain. Narcotics for pain management were required by 35 of 82 patients (43%).

Conclusions

A significant number of patients receiving sequential anthracycline/taxane–based chemotherapy for early-stage breast cancer experience pain, particularly during the taxane component. Prospective patient-reported outcome assessments are needed to help individualize treatment interventions and to improve symptom management in this population.     

18F-Fluorodeoxyglucose positron-emission tomography could have a prognostic role in patients with advanced hepatocellular carcinoma

Introduction

We set out to evaluate the prognostic value of ¹⁸F-fluorodeoxyglucose positron-emission tomography (pet) in patients with advanced (non-transplant-eligible) hepatocellular carcinoma (hcc) and to evaluate the correlation between standardized uptake values (suvs) and survival outcomes.

Methods

We identified patients with hcc who, from 2005 to 2013, underwent pet imaging before any treatment. This retrospective study from our hcc database obtained complete follow-up data for the 63 identified patients.

Results

Of the 63 patients, 10 underwent surgical resection, and 59 underwent locoregional therapy. In this cohort, 28 patients were pet-positive (defined as any lesion with a suv ≥ 4.0) before any therapy was given, and 35 patients were pet negative (all lesions with a suv < 4.0). On survival analysis, median survival was greater for the pet-negative than for the pet-positive patients: 29 months (range: 16.3–41.1 months) versus 12 months (range: 4.0–22.1 months) respectively, p = 0.0241. The pet-positive patients more often had large tumours (≥5 cm), poor differentiation, and extrahepatic disease, reflecting more aggressive tumours. On multivariate analysis, only pet positivity was associated with poor survival (p = 0.049).

Conclusions

Compared with pet-positive patients, pet-negative patients with hcc experienced longer survival. Imaging by pet can be of value in early prognostication for patients with hcc, especially patients receiving locoregional therapy for whom pathologic tumour differentiation is rarely available. This potential role for pet requires further validation in a prospective study.     

A population-based study of ethnicity and breast cancer stage at diagnosis in Ontario

Background

Breast cancer stage at diagnosis is an important predictor of survival. Our goal was to compare breast cancer stage at diagnosis (by American Joint Committee on Cancer criteria) in Chinese and South Asian women with stage at diagnosis in the remaining general population in Ontario.

Methods

We used the Ontario population-based cancer registry to identify all women diagnosed with breast cancer during 2005–2010, and we applied a validated surname algorithm to identify South Asian and Chinese women. We used logistic regression to compare, for Chinese or South Asian women and for the remaining general population, the frequency of diagnoses at stage ii compared with stage i and stages ii–iv compared with stage i.

Results

The registry search identified 1304 Chinese women, 705 South Asian women, and 39,287 women in the remaining general population. The Chinese and South Asian populations were younger than the remaining population (mean: 54, 57, and 61 years respectively). Adjusted for age, South Asian women were more often diagnosed with breast cancer at stage ii than at stage i [odds ratio (or): 1.28; 95% confidence interval (ci): 1.08 to 1.51] or at stages ii–iv than at stage i (or: 1.27; 95% ci: 1.08 to 1.48); Chinese women were less likely to be diagnosed at stage ii than at stage i (or: 0.82; 95% ci: 0.72 to 0.92) or at stages ii–iv than at stage i (or: 0.73; 95% ci: 0.65 to 0.82).

Conclusions

Breast cancers were diagnosed at a later stage in South Asian women and at an earlier stage in Chinese women than in the remaining population. A more detailed analysis of ethnocultural factors influencing breast screening uptake, retention, and care-seeking behavior might be needed to help inform and evaluate tailored health promotion activities.