Periodontal status and bacteremia with oral viridans streptococci and coagulase negative staphylococci in allogeneic hematopoietic stem cell transplantation recipients: a prospective observational study

Aim

This study was aimed to investigate whether any association could be found between the presence of an inflamed and infected periodontium (e.g., gingivitis and periodontitis) and the development of bacteremia during neutropenia following allogeneic hematopoietic stem cell transplantation (HSCT).

Methods

Eighteen patients underwent a periodontal examination before HSCT. Patients were classified as periodontally healthy [all periodontal pocket depths (PPD)?≤?4 mm and bleeding on probing (BOP)?≤?10 %) or as having gingivitis/periodontitis (PPD?≥?4 mm and BOP?>?10 %]. Oral mucositis (OM) was scored using the daily mucositis score. Blood cultures were taken at least twice weekly.

Results

Five patients were periodontally healthy, while 13 patients had gingivitis or periodontitis. Twelve patients (67 %) developed bacteremia during neutropenia, of which 11 patients (61 %) had one or more episodes of bacteremia due to coagulase-negative staphylococci (CONS, most often Staphylococcus epidermidis) or to oral viridans streptococci (OVS), or both. Patients with gingivitis/periodontitis more often had bacteremia than those with a healthy periodontium (p?=?0.047), and BOP was associated with bacteremia (p?=?0.049). All patients developed ulcerative OM, but its severity and duration were not associated with bacteremia. OM duration and the length of stay in the hospital were strongly correlated (R?=?0.835, p?≤?0.001).

Conclusion

This study indicates that periodontal infections may contribute to the risk of developing OVS and CONS bacteremia during neutropenia following HSCT. While our results point to the importance of periodontal evaluation and management before HSCT, further studies on periodontal contribution to systemic infectious complications are warranted.     

Clinical efficacy of adjunctive G-CSF on solid tumor and lymphoma patients with established febrile neutropenia

Background

The use of granulocyte colony-stimulating factor (G-CSF) as a prophylaxis against febrile neutropenia (FN) is well documented in the literature; however, the therapeutic use of G-CSF in the treatment of FN remains controversial. This study assessed the efficacy of adjunctive G-CSF in the treatment of FN by evaluating clinical outcomes.

Methods

This was a single-center, prospective cohort study conducted at the National Cancer Center in Singapore. Adult patients who had received chemotherapy and developed FN between January 2009 and January 2012 were included in the analysis. The clinical efficacy of adjunctive G-CSF was evaluated by investigating the duration of hospitalization, duration to absolute neutrophil count (ANC) recovery, duration of grade IV neutropenia, duration to fever resolution, duration of antibiotic therapy, and incidence of documented infections. A multivariate analysis was performed to identify patients who could potentially benefit from adjunctive G-CSF.

Results

Four hundred and thirty patients were analyzed. Majority manifested low-risk FN (81.2 %) based on the Multinational Association of Supportive Care in Cancer (MASCC) scoring. Compared to patients who did not receive adjunctive G-CSF, patients receiving adjunctive G-CSF had a nonsignificant reduction in the duration of hospitalization (3.5 vs. 3.7 days, p?=?0.41) and in ANC recovery time (3.4 vs. 3.5 days, p?=?0.76). Neutropenia-related mortality was lower among those who have received adjunctive G-CSF (2.4 vs. 8.4 %, p?=?0.006). Patients of Indian ethnicity and those who underwent gemcitabine-containing chemotherapy were less likely to receive adjunctive G-CSF treatment.

Conclusions

This observational study suggested that adjunctive G-CSF may confer clinical benefits among solid tumor and lymphoma patients with established febrile neutropenia. Further research should be conducted to validate the findings.     

Predictors of mortality attributable to Clostridium difficile infection in patients with underlying malignancy

Purpose

This study aimed at evaluating the clinical severity and treatment outcomes of Clostridium difficile infections (CDI) and identifying predictors associated with mortality in patients with malignancy.

Methods

A retrospective study was conducted in a teaching hospital from January 2004 to June 2013. The subjects included adult patients (aged ≥18 years) receiving treatment for malignancy whose conditions were complicated by CDI. Clinical severity was determined using the guidelines from the Society for Healthcare Epidemiology of America and the Infectious Diseases Society of America (SHEA/IDSA). Multivariate logistic regression analysis was performed to identify predictors independently associated with CDI-related mortality.

Results

Of the 5,594 patients treated for malignancy at the Division of Hematology/Oncology during the study period, 61 (1.1 %) had CDI complications. CDI-related mortality was 19.7 % (12/61). Twenty-seven (44.3 %) patients were diagnosed with neutropenia (ANC ≤500/mm³) at initial CDI presentation. Forty-one patients (67.2 %) received antimicrobial therapy for CDI. Based on the SHEA/IDSA guidelines, only 12 patients (19.7 %) presented with severe CDI, but 25 (61.0 %) patients experienced treatment failure. Multiple logistic regression modeling showed neutropenia to be an independent risk factor for CDI-related mortality (odds ratio, 5.17; 95 % confidence interval, 1.24–21.59).

Conclusions

This study tracked poor CDI treatment outcomes in patients with malignancy and identified neutropenia as a previously unrecognized risk factor of CDI-related mortality. Alternative definitions of severe CDI that include neutropenia might be necessary to more accurately determine clinical severity.     

Neutropenia management and granulocyte colony-stimulating factor use in patients with solid tumours receiving myelotoxic chemotherapy—findings from clinical practice

Purpose

Clinical practice adherence to current guidelines that recommend primary prophylaxis (PP) with granulocyte colony-stimulating factors (G-CSFs) for patients at high (≥20 %) overall risk of febrile neutropenia (FN) was evaluated.

Methods

Adult patients with breast cancer, non-small cell lung cancer (NSCLC), small-cell lung cancer (SCLC), or ovarian cancer were enrolled if myelotoxic chemotherapy was planned, and they had an investigator-assessed overall FN risk ≥20 %. The primary outcome was FN incidence.

Results

In total, 1,347 patients were analysed (breast cancer, n?=?829; NSCLC, n?=?224; SCLC, n?=?137; ovarian cancer, n?=?157). Patients with breast cancer exhibited fewer individual FN risk factors than patients with other cancers and were far more likely to have received a high-FN-risk chemotherapy regimen. However, a substantial proportion of all patients (45–80 % across tumour types) did not receive G-CSF PP in alignment with investigator risk assessment and guideline recommendations. FN occurred in 127 patients overall (9 %, 95% confidence interval (CI) 8–11 %), and incidence was higher in SCLC (15 %) than other tumour types (8 % in ovarian and NSCLC, 9 % in breast cancer). A post hoc analysis of G-CSF use indicated that G-CSF prophylaxis was not given within the recommended timeframe after chemotherapy (within 1–3 days) or was not continued across all cycles in 39 % of patients.

Conclusions

FN risk assessment was predominantly based on clinical judgement and individual risk factors, and guidelines regarding G-CSF PP for patients at high FN risk were not consistently followed. Improved education of physicians may enable more fully informed neutropenia management in patients with solid tumours.     

Outcomes in critically ill chronic lymphocytic leukemia patients

Background

Although recent studies have demonstrated an improvement in the prognosis of critically ill cancer patients, little is known regarding the prognosis of patients with non-aggressive underlying malignancies. The aims of this study were to assess the prognosis of critically ill patients with chronic lymphocytic leukemia (CLL) and to evaluate risk factors for hospital mortality.

Methods

In retrospective mono-center cohort study, consecutive adult patients with CLL requiring ICU admission from 1997 to 2008 were included.

Results

Sixty-two patients of 67 years (62–75) were included. Median time interval between CLL diagnosis and ICU admission was 6.7 years (2.6–10.8). Nine patients (15 %) had stage C disease at the time of ICU admission, and seven patients (11 %) had Richter syndrome. Most ICU admissions were related to bacterial or fungal pulmonary infections (n?=?47; 76 %). ICU, in-hospital, and 90-day mortality were 35 % (n?=?22), 42 % (n?=?26), and 58 % (n?=?36), respectively. Only three factors were independently associated with in-hospital mortality: oxygen saturation lower than 95 % when breathing room air (odds ratio (OR) 5.80; 95 % confidence interval (CI) 1.23–27.33), need for vasopressors (OR 27.94; 95 % CI 5.37–145.4), and past history of infection (OR 6.62; 95 % CI 1.34–32.68). The final model did not change when disease-related variables (Binet classification, Richter syndrome, long-term steroids) or treatment-related variables (fludarabine, rituximab, or alemtuzumab) were included.

Conclusion

Acute pulmonary infections remain the leading cause of ICU admission in patients with CLL. The severity at ICU admission and past history of infection were the only factors associated with hospital mortality. Neither disease characteristics nor previous cancer treatments were associated with outcome.     

Efficacy and safety of early G-CSF administration in patients with head and neck cancer treated by docetaxel-cisplatin and 5-fluorouracil (DCF protocol): a retrospective study

Background

Induction chemotherapy with docetaxel-cisplatin and 5-fluorouracil (DCF) for locally advanced head and neck cancers (HNC) is associated with a high risk of severe neutropenia or febrile neutropenia (FN). We conducted a retrospective study to evaluate the efficacy and safety of administering granulocyte colony-stimulating factor (G-CSF) on day 3 (D3) during chemotherapy (early G-CSF stimulation) versus after the end of chemotherapy, as per current guidelines (i.e., after the end of 5-FU perfusion; D7), and its impact on patient outcomes.

Patients and methods

Patients ≥19 years old, with advanced HNC who received DCF induction chemotherapy (D and P 75 mg per meter squared (mg/m²) on day 1 and 5-FU 750 mg/m²/day from D1 to D5), were included in the analysis.

Results

Data of 70 patients were analyzed from 01 January 2003 to 01 December 2010. Mean age was 56 years (range 45 to 77 years). Thirty-six patients (51.4 %) received pegfilgrastim on D7, and 28 (40 %) started G-CSF prophylaxis during chemotherapy; 12 (17.1 %) had daily filgrastim and 16 (22.9 %) pegfilgrastim on D3. Overall response rate (ORR) was 89.6 % (three early deaths due to infectious complications; 4.3 %). The 3-year overall survival (OS) rate was 72.8 %. FN rate was 14.3 % and chemotherapy delay was 12.9 %. In the D7 G-CSF arm, incidence of grade 3–4 neutropenia (p?=?0.023), FN (p?=?0.029), and cycle delays (p?=?0.006) was statistically higher than the “early” G-CSF arm. A decrease of OS was observed at 2 years (from 85.1 to 63.5 %) of chemotherapy discontinuation or FN (p?=?0.0348).

Discussion

Early administration of G-CSF is safe and seems to be more effective than D7. Future prospective trials are required to confirm our results.     

Topical agent therapy for prevention and treatment of radiodermatitis: a meta-analysis

Background

Radiodermatitis (RD) is a common side effect during radiotherapy. Various topical agents have been tried to be applied on RD. However, the efficiency of topical agents applied on radiotherapy is still uncertain.

Objective

This study aims to assess the efficiency of the topical agents in the prevention and treatment of RD.

Methods

The Cochrane Central Register of Controlled Trials, Pubmed, and Medline were searched for relevant reports. Quantitative analysis was carried out to evaluate the efficiency of topical agents in the prevention and treatment of RD.

Results

Twenty reports involving 3,098 patients were included: 2,406 patients for prophylactic trials and 692 for treatment trials, respectively. For prophylactic trials, primary meta-analysis indicated that using topical agents could not reduce the incidence of grade 2 and higher RD (P?=?0.128, RR?=?0.90, 95 % CI?=?0.78–1.03) with a high heterogeneity (P?=?0.000, I ²?=?71.5 %). In subgroup analyses, heterogeneity disappeared by excluding reports with low Jadad score (≤3) (P?=?0.292, I ²?=?15.2 %), and still no significant difference was found between the topical agent group and control group (P?=?0.625, RR?=?0.98, 95 % CI?=?0.89–1.07). In addition, for treatment trials, topical agents failed to increase the incidence of wound healing (P?=?0.784, RR?=?1.01, 95 % CI?=?0.92–1.12) with a high heterogeneity (P?=?0.067, I ²?=?51.5 %).

Conclusions

Topical agents could not prevent or treat RD effectively. New type of agents should be developed to improve the efficiency based on the pathophysiology of RD.     

Characteristics of unplanned hospital admissions due to drug-related problems in cancer patients

Background

Studies have examined drug-related problems (DRPs) that have led to hospital admissions in the general population. However, there is a lack of information on the characteristics of DRPs in the cancer population.

Objective

The objective of this study was to investigate the type, causality, severity, and preventability of DRPs that result in unplanned hospitalizations among cancer patients.

Methods

This was a prospective, cohort study conducted in two oncology wards between July and December 2012. All patients who were diagnosed with solid tumor or lymphoma and required unplanned hospitalization were included. The incidence of DRPs among hospital admissions was captured, and the nature of the DRPs (causality, severity, and preventability) was characterized.

Results

There were 1,299 admissions and 1,275 were eligible for analysis. Among the 1,275 eligible admissions, 158 (12.4 %) were considered to be associated with a DRP. In the 158 admissions associated with DRPs, 164 DRPs were found. The majority of the DRP-related admissions were adverse drug reactions (ADRs) (n?=?155/164, 94.5 %), probable (n?=?98, 59.8 %), moderately severe (n?=?155, 94.5 %), and probably or definitely preventable (n?=?86, 52.4 %). Most patients with DRPs recovered and were discharged. Febrile neutropenia was the most common adverse drug reaction, and drug combinations involving antihypertensives and long-term corticosteroids raised the risks for potential drug-drug interactions among patients with cancer.

Conclusion

The incidence of DRP-induced unplanned hospital admissions was 12.4 % among cancer patients. Approximately half of these were preventable events.     

Serious postoperative infections following resection of common solid tumors: outcomes, costs, and impact of hospital surgical volume

Purpose

Unlike infections related to chemotherapy-induced neutropenia, postoperative infections occurring in patients with solid malignancy remain largely understudied. Our aim is to evaluate the outcomes and the volume–outcomes relationship associated with postoperative infections following resection of common solid tumors.

Methods

We used Texas Discharge Data to study patients undergoing resection of cancer of the lung, esophagus, stomach, pancreas, colon, or rectum from 01/2002 to 11/2006. From their billing records, we identified ICD-9 codes indicating a diagnosis of serious postoperative infection (SPI), i.e., bacteremia/sepsis, pneumonia, and wound infection, occurring during surgical admission or leading to readmission within 30 days of surgery. Using regression-based techniques, we estimated the impact of SPI on mortality, resource utilization, and costs, as well as the relationship between hospital volume and SPI, after adjusting for confounders and data clustering.

Results

SPI occurred following 9.4 % of the 37,582 eligible tumor resections and was independently associated with nearly 12-fold increased odds of in-hospital mortality [95 % confidence interval (95 % CI), 7.2–19.5, P?<?0.001]. Patients with SPI required six additional hospital days (95 % CI, 5.9–6.2) at an incremental cost of $16,991 (95 % CI, $16,495–$17,497). Patients who underwent resection at high-volume hospitals had a 16 % decreased odds of developing SPI than those at low-volume hospitals (P?=?0.03).

Conclusions

Due to the substantial burden associated with SPI following common solid tumor resections, hospitals must identify more effective prophylactic measures to avert these potentially preventable infections. Additional volume–outcomes research is needed to identify infection prevention processes that can be transferred from high- to lower-volume providers.     

Which patients with advanced cancer and biliary obstruction benefit from biliary stenting most? An analysis of prognostic factors

Background

Patients with advanced cancer may present with obstructive jaundice. Biliary stenting is the treatment of choice. However, which patients benefit most is not well-defined, yet. Our aim was to delineate the clinical factors affecting prognosis.

Material and methods

Charts of 140 patients with advanced cancer who underwent biliary stenting were retrospectively analyzed. Their median age was 63.5 years. Of these patients, 73 (52.1 %) were male, 32 (22.9 %) had ECOG PS 1 and 81 (57.9 %) had PS 2. The most frequent cancer types were cholangiocellular cancer (64, 45.7 %) and pancreatic cancer (36, 25.7 %).

Results

Median overall survival (OS) was 141 (95 % CI, 100.7-185.3) days. Female patients lived longer (161.0 vs. 124.0 days) (p?=?0.036). Those patients with colorectal cancer lived the longest (667.0 days), followed by cholangiocellular (211.0 days), and gastric cancers (106.0 days) (p?=?0.004). The distribution of primary diagnosis differed significantly between sexes: cholangiocellular cancer was present in 22 (30.1 %) out of 73 men and 42(62.7 %) out of 67 women (chi-square p?<?0.001). There was a trend for longer overall survival if ALT (p?=?0.08) and AST (p?=?0.06) were normalized after stent insertion. Of the 137 patients, 63 (45.5 %) did not experience any complication. In 74 patients with complications, there were 39 (28.5 %) episodes of cholangitic infections and 35 (25.5 %) biliary obstructions. In three patients, we could not find data on infections.

Conclusion

Underlying malignancy, hence the natural biology and the therapeutic expectations are probably the most important factors which must be considered during decision-making.     

Complementary and alternative medicine use and disclosure amongst Australian radiotherapy patients

Purpose

Information on complementary and alternative medicine (CAM) use in Australian radiotherapy patients is sparse. This study investigated the type and prevalence of CAM amongst an Australian regional radiotherapy patient cohort and the disclosure of information to the consultant radiation oncologist.

Methods

A single hardcopy questionnaire survey was provided to patients regarding the use of CAM and discussion with the treating medical practitioner. The National Centre for Complementary and Alternative Medicine (NCCAM) classification was used to group responses. The study was open for a period of 4 months, and all patients on treatment during this period were approached.

Results

A total of 170 questionnaires were distributed to eligible patients, and 152 patients returned a completed questionnaire (89.4 % response rate). Sixty-nine of the 152 patients (45.4 %) reported active CAM use. Of the 69 patients who used CAM, mind–body medicine (n?=?54, 78.3 %) and biological-based therapies (n?=?54, 78.3 %) were the commonest NCCAM group, whilst manipulative/body-based therapies (n?=?44, 63.8 %), whole medical systems (n?=?7, 10.1 %) and energy therapies (n?=?5, 7.2 %) were the least common. The most common therapies were vitamins and mineral supplementation (n?=?33, 47.8 %) and massage therapy (n?=?18, 26.1 %). Of note, only 29 participants stated that they had discussed CAM therapies with their radiation oncologist.

Conclusions

CAM use was prevalent amongst cancer patients undergoing radiotherapy, but frequently not discussed with the treating radiation oncologist. Considering the high prevalence of CAM, further resources could be justifiably directed at providing this service for cancer patients to foster a more holistic approach to their care.     

A descriptive study of persistent oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer

Background

Prolonged neurotoxicity after systemic chemotherapy has the potential to impact on quality of life. We explored the frequency of persistent peripheral neuropathy in patients who received oxaliplatin for colorectal cancer at two local centres.

Patients and methods

Questionnaires were sent to patients who completed treatment with oxaliplatin for colorectal cancer at least 20 months prior to entering the study. Neuropathy questions were adapted from the FACT/GOG-Ntx (V.4) questionnaire.

Results

Of the 56 eligible patients, 27 returned the questionnaire. Twenty-five patients (93 %) experienced neuropathic symptoms during their treatment; 11 had grade-2, and two had grade-3 symptoms. At the time of completing the questionnaire, 17 patients (63.0 %; 95%CI 43.9–79.4 %) were still symptomatic with 12 patients (44.4 %; 95%CI 26.8–63.3) having grade-2 or grade-3 symptoms and three patients (11.1 %; 95%CI 2.9–27.3) having grade-3 neuropathic symptoms. Participants who received more than 900 mg/m² oxaliplatin had a significantly higher risk of persistent grade-2 or grade-3 neuropathy (p?=?0.031, RR?=?8.3 95%CI?=?1.2–57.4). There was a trend toward increased risk of persistent neuropathy of any grade among participants with a history of regular alcohol use (p?=?0.051; RR?=?1.7 95%CI 1.0–2.8).

Conclusion

Persistent oxaliplatin-induced neuropathy is not as uncommon as previously suggested, and the rate of grade-2 and grade-3 symptoms could be considerably higher than previous reports.     

Physical exercise and therapy in terminally ill cancer patients: a retrospective feasibility analysis

Purpose

Physical exercise (PE) and/or therapy (PT) shows beneficial effects in advanced cancer patients and is increasingly implemented in hospice and palliative care, although systematic data are rare. This retrospective study systematically evaluated the feasibility of PE/PT in terminally ill cancer patients and of different modalities in correspondence to socio-demographic and disease- and care-related aspects.

Methods

All consecutive terminally ill cancer patients treated in a palliative care inpatient ward during a 3.5-year period were included. The modalities were chosen according to the therapists' and patients' appraisal of current performance status and symptoms.

Results

PE/PT were offered to 572 terminally ill cancer patients, whereof 528 patients (92 %) were able to perform at least one PE/PT unit (average 4.2 units/patient). The most frequently feasible modalities were physical exercises in 50 %, relaxation therapy in 22 %, breathing training in 10 %, and positioning and lymph edema treatment in 6 % each. Physical exercise and positioning treatment were performed significantly more often in older patients (p?=?0.009 and p?=?0.022, respectively), while relaxation (p?=?0.05) and lymph edema treatment (p?=?0.001) were used more frequently in younger. Breathing training was most frequently performed in head and neck cancer (p?=?0.002) and lung cancer (p?=?0.026), positioning treatment in brain tumor patients (p?=?0.021), and lymph edema treatment in sarcoma patients (p?=?0.012).

Conclusions

PE/PT were feasible in >90 % of terminally ill cancer patients to whom PE/PT had been offered. Physical exercises, relaxation therapy, and breathing training were the most frequently applicable methods. Prospective trials are needed to evaluate the efficacy of specific PE/PT programs in terminally ill cancer patients.     

Basal renal function reserve and mean kidney dose predict future radiation-induced kidney injury in stomach cancer patients

Background

Adjuvant chemoradiotherapy (CRT) improves the survival in patients with locally advanced stomach cancer. The kidneys are the major dose-limiting organs for radiotherapy (RT) in upper abdominal cancers. We aimed to evaluate the impact of adjuvant CRT on renal function of patients with stomach cancer.

Material and methods

Fifty-nine stomach cancer patients who underwent postoperative CRT were included. Demographic parameters (age, gender), and basal and 12th-month biochemical parameters were recorded. Mean kidney dose (MKD) administered was determined. Estimated glomerular filtration rate (eGFR) was calculated by modification of diet in renal disease formula.

Results

Fifty-nine patients were recruited (age 60.8?±?11.9 years; female/male 25/34; follow-up duration 15.6?±?9.8 months). Twenty-one patients (35.6 %) had basal eGFR <90 ml/min/1.73 m². When the basal and 12th-month eGFR was compared, eGFR decreased in 27 patients (45.8 %), whereas eGFR remained stable in 32 (54.2 %) patients. Cox regression analyses revealed that a MKD ≥1,500 cGy and basal eGFR <90 ml/min/1.73 m² significantly increased the risk of a decreased eGFR at 12th month (HR?=?2.288, 95 % CI 1.009–5.188, p?=?0.048 and HR?=?2.854, 95 % CI 1.121–7.262, p?=?0.028, respectively).

Conclusion

MKD ≥1,500 cGy and a basal eGFR <90 ml/min/1.73 m² significantly increased the risk of a decreased eGFR at 12th month. We suggest that patients with stomach cancer be evaluated for their basal renal reserve prior to RT, and it may be more convenient to further minimize the dose to the kidneys with more sophisticated RT techniques in patients with stomach cancer, more specifically in patients with decreased renal reserve.     

HSV-1 as well as HSV-2 is frequent in oral mucosal lesions of children on chemotherapy

Purpose

Prevalence data of herpes simplex virus (HSV) in oral mucositis in children on treatment for cancer is limited. Quantitative polymerase chain reaction (PCR) has been seldom utilized for detection of HSV-1/2 in oral mucosa.

Methods

Children on treatment for cancer with oral mucositis were enrolled as cases and healthy children as controls. An oral swab from the lesion in cases and mucosal scraping in controls were obtained. Both qualitative and real-time quantitative PCR for HSV-1/2 were performed. Serum ELISA-IgG/IgM for HSV-1/2 antibodies (NovaLisa?-Dietzenbach-Germany) were measured.

Results

Thirty-two cases (Age, 6.3?±?3.4 years) and 30 controls were enrolled. Majority (69 %) of cases had ALL. All patients had febrile neutropenia, except two. ELISA-IgM-HSV-1/2 was not positive in any case or control. ELISA-IgG-HSV-1/2 was positive in 11 (34 %) cases and nine (30 %) controls (p?=?1.0). Qualitative PCR for HSV-1 detected the virus in eight (25 %) cases and nil controls (p?=?0.009). HSV-2 was not detected in any case/control by qualitative PCR. Quantitative PCR detected HSV-1 in 21 (66 %) and HSV-2 in 22 (69 %) cases. In controls, quantitative PCR detected HSV-1 in three (10 %) and HSV-2 in none. In patients, the mean viral load of HSV-1 (5,500?±?15,987?×?10⁴ copies/nanogram DNA) was more than HSV-2 (4.03?±?8.5?×?10⁴) (p?=?0.11). There was no correlation of HSV-1/2 with grading of mucositis.

Conclusions

Both HSV-1/2 are commonly shed from oral mucosal lesions in children receiving chemotherapy. In a novel finding, real-time PCR detected copies of HSV-2 in 69 % cases, all missed by conventional PCR. Implication for morbidity, if any, or treatment needs to be determined.     

Comparison of pegfilgrastim on day?2 vs. day?4 as primary prophylaxis of intense dose-dense chemotherapy in patients with node-positive primary breast cancer within the prospective, multi-center GAIN study: (GBG 33)

Background

Preliminary data suggest that pegfilgrastim given on day?4 (P4) might be superior to pegfilgrastim on day?2 (P2) in reducing grade 4 leucopenia.

Methods

Patients with node-positive primary breast cancer receiving epirubicin?Cpaclitaxel?Ccyclophosphamide chemotherapy were randomized to receive P2 versus P4. Primary endpoint was leucopenia grade 4, assuming a risk reduction of 50% with P4 from 50% in P2 to 25% with P4.

Results

Three-hundred fifty-one patients were randomized to P2 (n?=?174) versus P4 (n?=?177). The rate of leucopenia (grade 4) was 47.1% with P2 and 42.0% with P4 (p?=?0.387), neutropenia (grade 3?+?4) was 47.9% versus 40.8% (p?=?0.337), FN was 4.7% versus 8.0% (p?=?0.271), and infections was 29.9% versus 25.4% (p?=?0.404), respectively.

Conclusion

This study failed to demonstrate that pegfilgrastim on day?4 was more efficacious than on day?2 with respect to grade 4 leucopenia (the primary endpoint), febrile neutropenia, or infections.     

Characteristics and outcomes of advanced cancer patients who miss outpatient supportive care consult appointments

Background

Missed appointments (MA) are frequent, but there are no studies on the effects of the first MA at supportive care outpatient clinics on clinical outcomes.

Methods

We determined the frequency of MA among all patients referred to our clinic from January–December 2011 and recorded the clinical and demographic data and outcomes of 218 MA patients and 217 consecutive patients who kept their first appointments (KA).

Results

Of 1,352 advanced-cancer patients referred to our clinic, 218 (16 %) had an MA. The MA patients’ median age was 57 years (interquartile range, 49–67). The mean time between referral and appointment was 7.4 days (range, 0–71) for KA patients vs. 9.1 days (range, 0–89) for MA patients (P?=?0.006). Reasons for missing included admission to the hospital (17/218 [8 %]), death (4/218 [2 %]), appointments with primary oncologists (37/218 [18 %]), other appointments (19/218 [9 %]), visits to the emergency room (ER) (9/218 [9 %]), and unknown (111/218 [54 %]). MA patients visited the ER more at 2 weeks (16/214 [7 %] vs. 5/217 [2 %], P?=?0.010) and 4 weeks (17/205 [8 %] vs. 8/217 [4 %], P?=?0.060). Median-survival duration for MA patients was 177 days (range, 127–215) vs. 253 days (range, 192–347) for KA patients (P?=?0.013). Multivariate analysis showed that MAs were associated with longer time between referral and scheduled appointment (odds ratio [OR], 1.026/day, P?=?0.030), referral from targeted therapy services (OR, 2.177, P?=?0.004), living in Texas/Louisiana regions (OR, 2.345, P?=?0.002), having an advanced directive (OR, 0.154, P?P?=?0.0003).

Conclusion

MA patients with advanced cancer have worse survival and increased ER utilization than KA patients. Patients at higher risk for MA should undergo more aggressive follow-up. More research is needed.     

Use of bisphosphonates and the risk of osteonecrosis among cancer patients: a systemic review and meta-analysis of the observational studies

Purpose

This study aims to systematically review observational studies evaluating the use of bisphosphonates (BPs) and risk of osteonecrosis of the jaw (ONJ) among cancer patients.

Methods

PubMed, Embase, and Cochrane Library were screened from database inception to Aug 2012. Two reviewers independently identified cohort and case–control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals were derived by random effects meta-analysis. Subgroup analyses were carried out according to patients’ characteristics and route of BP use.

Results

We identified eight studies, including 1,389 cases and 569,620 controls. Use of BPs was associated with a significantly increased risk of ONJ (odds ratio (OR) 4.25; 95 % confidence interval (CI) 3.67–5.36; I ²?=?0 %). The summary OR was 4.22 (95 % CI 3.21–5.54; I ²?=?0 %) for adjusted studies. IV BPs were associated with higher risk (OR 4.27; 95 % CI 3.38–5.40; I ²?=?0 %) than oral BPs (OR 1.18; 95 % CI 0.89–1.56; I ²?=?0 %). Hospital-based studies were associated with higher risk estimates than population-based studies.

Conclusion

The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at the highest risk. It is important to assess oral health before initiating therapy and to avoid dental procedures during the active phase of intravenous BP therapy.     

Bacteria causing bacteremia in pediatric cancer patients presenting with febrile neutropenia—species distribution and susceptibility patterns

Purpose

Infections are a major cause of morbidity and mortality in pediatric cancer patients. The aim of this study was to establish the microbiological spectrum and the susceptibility patterns of bacteremia-causing bacteria in pediatric cancer patients with febrile neutropenia in relation to the use of prophylactic and empirical antibiotics.

Methods

We analyzed positive blood cultures of pediatric cancer patients presenting with febrile neutropenia between 2004 and 2011 in Groningen and Amsterdam (the Netherlands) and in Bern (Switzerland), using different antibiotic prophylactic and empirical regimens.

Results

A total of 156 patients with 202 bacteremias, due to 248 bacteria species, were enrolled. The majority (73 %) of bacteremias were caused by Gram-positive bacteria. Gram-negative bacteria, especially Pseudomonas aeruginosa, were observed significantly more often in Bern, where no fluoroquinolone prophylaxis was used. Ciprofloxacin-resistant bacteria were cultured more often from patients who did receive ciprofloxacin prophylaxis, compared to the patients who did not (57 versus 11 %, p?=?0.044).

Conclusions

Gram-positive bacteria predominated in this study. We showed that the use of prophylactic antibiotics in pediatric cancer patients was associated with increased resistance rates, which needs further study. The strategy for empiric antimicrobial therapy for febrile neutropenia should be adapted to local antibiotic resistance patterns.     

Impact of oral mucositis on short-term clinical outcomes in paediatric and adolescent patients undergoing chemotherapy

Purpose

The purpose of this study is to determine the burden of the peak severity of oral mucositis and severity over time on selected clinical outcomes in paediatric and adolescent patients receiving chemotherapy.

Patients and methods

A multicentre study enrolled 140 patients between the ages of 6 and 18 years, who had been treated with chemotherapy and completed the self-report Mouth and Throat Soreness-related questions of the Oral Mucositis Daily Questionnaire for 14 days. Clinical data were collected from patients' medical records during the first 14 days after starting chemotherapy.

Results

Forty-one percent developed oral mucositis. Multiple linear regression analysis revealed that oral mucositis was significantly associated with an increased loss of baseline body weight, after controlling for nausea/vomiting (β?=?0.34, p?=?0.002). Multiple logistic regression analysis showed that severe mucositis was significantly associated with a higher probability of fluid replacement, after controlling for nausea/vomiting (adjusted OR?=?12.8; 95 % CI?=?2.7–61.0; p?=?0.001). In addition, severe mucositis was significantly associated with a higher probability of fever, after controlling for neutropoenia (adjusted OR?=?5.4; 95 % CI?=?1.8–15.4; p?=?0.002). No difference was observed for oral or systemic infections among the subgroups. About 5 % of the patients with oral mucositis had delays in chemotherapy (≤7 days). None of the patients had dose modification or unplanned hospitalization due to oral mucositis. The associations of peak severity and overall oral mucositis with adverse clinical outcomes in paediatric and adolescent patients were equivalent.

Conclusion

Oral mucositis is associated with negative effects on clinical outcomes.