Use of low-level laser therapy (LLLT) or photobiomodulation (PBM) for the management of the hand-foot syndrome (HSF) or palmo-plantar erythrodysesthesia (PPED) associated with cancer therapy.

The purpose of this pilot study was to determine whether photobiomodulation (PBM) might be effective for chemotherapy-induced palmo-plantar erythrodyesthesia (PPED), as it is for mucositis or radio dermatitis; no standard therapy exists for PPED. Patients were allocated to PBM or sham irradiation and were blindly assessed after 2 weeks. Pain and satisfaction with treatment were also evaluated. We found a significant benefit from PBM in comparison with sham treatment (p < 0.03) and a decrease of pain in 49% of the patients. No adverse reactions were observed. We concluded that PBM might represent a useful approach for the management of PPED.

Retrospective evaluation of the safety of low-level laser therapy/photobiomodulation in patients with head/neck cancer.

BACKGROUND: The standard therapeutic approach for locally advanced head and neck cancer is optimal use of radiation therapy with or without concomitant chemotherapy. The most common and distressing acute complication of such therapies is oral/pharyngeal mucositis that may be associated with severe morbidity and can interfere with the planned administration of therapy. METHODS: We have identified all patients diagnosed with head/neck cancer between 2005 and 2009, having received radiotherapy with or without cisplatin-based chemotherapy. Radiotherapy consisted of intensity-modulated radiation therapy (IMRT) in all patients. In patients with grade > 2 mucositis, photobiomodulation (PBM) consisted of three sessions of low-level laser irradiation weekly, in accordance with recently published recommendations for PBM. Patients who did not receive PBM were those for whom that approach was not requested by the radiotherapists and those who declined it. RESULTS: Two hundred twenty-two patients (62%) received PBM and 139 did not (39%). The patient's characteristics were equally distributed between the two groups. For overall survival, time to local recurrence, and progression-free survival, there was no statistical evidence for a difference in prognosis between patients with and without PBM. In a multivariate analysis, after adjusting for known prognostic factors, we found no statistical evidence that PBM was related to overall survival, progression-free survival, or local recurrence. CONCLUSIONS: Our results show evidence of no effect of PBM upon overall survival, time to local recurrences, and disease-free survival of patients with head and neck cancer treated with radiotherapy with/without chemotherapy.

Predictive factors for cancer-associated thrombosis in a large retrospective single-center study.

BACKGROUND: The relationship between cancer and thrombosis has been studied for years, but reliable guidelines for thromboprophylaxis in that situation are still unclear. METHODS: We retrospectively reviewed the files of 3159 consecutive patients with newly diagnosed solid tumors at Jules Bordet Institute from January 2008 to December 2011. Among them, 99 developed a symptomatic thromboembolic episode and were matched with 2 controls (nested case control). The aim was to identify risk factors of thromboembolic events and to validate in our setting the Khorana score. RESULTS: In the cohort study, nodal status ≥ 2, presence of metastases, and primary tumor site were found to be the most significant predictive factors of a thromboembolic event (n = 99; 3.1%) in the multivariate analysis. In the nested study (n = 265), hemoglobin < 13 g/dL or treatment with a red cell growth factor, CRP ≥ 31.6 mg/L, creatinine level > 0.96 mg/dL, chronic inflammatory disease, and personal or familial history of thromboembolic events were found to be the most significant predictive factors of a thromboembolic event in the multivariate analysis. In our population, the sensitivity, specificity, positive predictive value, and negative predictive value of the Khorana score were respectively 29%, 93%, 15%, and 96%. CONCLUSION: We confirm the value of the risk factors identified in the literature with the additional presence of nodal involvement, elevated CRP, and creatinine levels, which may be helpful for patient risk stratification and should be considered in future clinical trials. Our results also suggest that the Khorana score might help to identify patients who can safely be spared of thromboprophylaxis.

Intravenous iron therapy for anemic cancer patients: a review of recently published clinical studies.

Based on available literature and on the present review, IV iron administration to anemic cancer patients can increase significantly the level of Hb, probably independently from the precise mechanism of anemia itself. However, in future studies, the benefit should be evaluated taking into account whether the anemia is due to absolute or functional iron deficiency; therapeutic modalities might be different for these two conditions. Along the same lines, it appears important to further evaluate the respective roles of PO and IV iron therapies and the modalities of their use in clinical practice. Until the results of such studies are available, it appears reasonable to propose IV iron therapy to anemic cancer patients as the resulting rise of Hb level may increase their quality of life and performance status and reduce the need for erythropoietin-stimulating agents and/or blood transfusions.

Bisphosphonate-related osteonecrosis of the jaw: a review of the potential efficacy of low-level laser therapy.

Osteonecrosis of the jaw (ONJ) resulting from administration of bisphosphonates (BP) or denosumab is a rare but severe complication in cancer patients. Complete remission depends on the stage of ONJ; it can be estimated in the range of 20-30 %. Low-level laser therapy (LLLT) is a logical additional option, as it has been recognized effective for the management of chemotherapy and/or radiotherapy-induced mucositis. LLLT irradiation has anti-inflammatory actions and thus can help to control pain, as well as biostimulating properties with favorable actions on bacterial control and wound healing. We review the results of seven published studies of LLLT in BP-associated ONJ. LLLT results in an overall response rate of 55 % superior to that observed in controls (30 %). Our review suggests that there might be an advantage to add LLLT to the "classical" management of ONJ. This therapy is easy to administer and is not associated with any known side effects. Further research is needed to remove any doubt of protection or enhancement of carcinogenic processes. We believe that prospective well-controlled studies of LLLT in ONJ are warranted. If the positive results are confirmed, it would represent a great improvement for the quality of life of many patients.

Predictors of physicians' satisfaction with their management of uncertainty during a decision-making encounter with a simulated advanced stage cancer patient.

OBJECTIVES: To optimize their training, predictors of physicians' satisfaction with their management of uncertainty should be examined. This study investigated these predictors by using a simulated advanced stage cancer patient. METHODS: Physicians (n=85) rated their satisfaction with their management of uncertainty (Visual Analog Scale-100mm) after a decision-making encounter. Communication predictors were examined with the: Observing Patient Involvement scale (OPTION), Multidimensional analysis of Patient Outcome Predictions (MD.POP) and Communication Content Analysis Software (LaComm). Psychological predictors were assessed with the: Intolerance of Uncertainty Inventory (IUI), Physicians' Reactions to Uncertainty scale (PRU), Decisional Conflict Scale (DCS), and Jefferson Scale of Physician Empathy (JSPE). RESULTS: Physicians' satisfaction (mean=67mm; standard deviation=17mm) was not predicted by their communication, but by their anxiety due to uncertainty (PRU) (ß=-.42; p=<.001) and their perceived empathy (JSPE) (ß=.26; p=.009). These variables accounted for 25% of variance in physicians' satisfaction. CONCLUSIONS: Physicians' satisfaction with their management of uncertainty was not affected by their communication performance, but by their psychological characteristics. PRACTICE IMPLICATIONS: Training programs should increase physicians' awareness regarding the communication performance required in decision-making encounters under conditions of uncertainty.

Fever of unknown origin in cancer patients.

Fever of unknown origin (FUO) remains a challenging clinical problem, namely in patients with cancer. In cancer patients, FUO may be due to the cancer itself, as it is the case of hematological malignancies; digestive tumors (colon cancer, liver metastases) are significantly associated with FUO and infection can be demonstrated in some cases. Prevention with G-CSF and empirical antimicrobial therapy are essential approaches for the management of FUO in cancer patients. New diagnostic approaches, such as PET imaging, should be further evaluated in cancer patients with FUO.

A general chemotherapy myelotoxicity score to predict febrile neutropenia in hematological malignancies.

BACKGROUND: Chemotherapy-induced neutropenia is the most common adverse effect of chemotherapy and is often complicated by febrile neutropenia (FN). The objective of this study is to validate a classification of aggressiveness of a chemotherapy regimen and to evaluate its usefulness in a risk prediction model of FN in patients with hematological cancer at the beginning of a chemotherapy cycle. PATIENTS AND METHODS: Two hundred and sixty-six patients were prospectively enrolled and followed during 1053 cycles. Relevant patient informations were collected at the beginning of the first cycle and the number of days of FN were counted in the follow-up [dichotomized (no FN versus >or= 1 day of FN)]. RESULTS: Aggressive chemotherapy regimen is the major predictor of FN [odds ratio 5.2 (3.2-8.4)]. The other independent predictors are the underlying disease, an involvement of bone marrow, body surface

The use of low-energy laser (LEL) for the prevention of chemotherapy- and/or radiotherapy-induced oral mucositis in cancer patients: results from two prospective studies.

BACKGROUND: Low-energy laser (LEL) treatment has been suggested as an effective and safe method to prevent and/or treat oral mucositis induced by chemotherapy and/or radiotherapy; however, it has not gained wide acceptance so far. MATERIALS AND METHODS: We conducted two clinical trials testing the LEL technique: firstly, as a secondary prevention in patients with various solid tumors treated with chemotherapy who all developed severe mucositis after a previous identical chemotherapy and, secondly, as therapeutic intervention (compared to sham illumination in a randomized way) in patients with hematological tumors receiving intensive chemotherapy and having developed low-grade oral mucositis. RESULTS: We entered 26 eligible patients in the first study and 36 were randomized in the second study. The success rate was 81% (95%CI = 61-93%) when LEL was given as a preventive treatment. In the second study, in patients with existing lesions, the therapeutic success rate was 83% (95%CI = 59-96%), which was significantly different from the success rate reached in the sham-treated patients (11%; 95%CI = 1-35%); the time to development of grade 3 mucositis was also significantly shorter in the sham-treated patients (p < 0.001). CONCLUSION: Our results strongly support the already available literature, suggesting that LEL is an effective and safe approach to prevent or treat oral mucositis resulting from cancer chemotherapy.

Bacteraemia in febrile neutropenic cancer patients.

A total of 2142 patients with febrile neutropenia resulting from cancer chemotherapy were registered in two observational studies and followed prospectively in different institutions. There were 499 (23%) patients with bacteraemia who are reviewed here. The relative frequencies of Gram-positive, Gram-negative and polymicrobial bacteraemias were 57%, 34% and 10% with respective mortality rates of 5%, 18% and 13%. Mortality rates were significantly higher in bacteraemic patients than in non-bacteraemic patients; a trend for higher mortality was observed (without reaching statistical significance) in those patients in whom bacteraemia was associated with a clinical site of infection compared to bacteraemic patients without any clinical documentation. Prophylactic antibiotics but not granulopoiesis stimulating factors were associated with a lower incidence of Gram-negative bacteraemia; however, neither prophylactic approach influenced the subsequent rate of complications in the patients who developed bacteraemia. The present study also confirms that the MASCC scoring system can identify a group of bacteraemic patients with a relatively low risk of complications and death (MASCC >/=21). On the other hand, in patients with very low levels of the MASCC score (<15), and then with predicted very unfavourable risk, the rate of complications and death was dramatically high, irrespective of the microbiological nature of the bacteraemia.

Low mannose-binding lectin concentration is associated with severe infection in patients with hematological cancer who are undergoing chemotherapy.

BACKGROUND: Mannose-binding lectin (MBL) is a serum lectin involved in innate immune response. Low serum MBL concentration may constitute a risk factor for infection in patients receiving myelosuppressive chemotherapy. METHODS: We conducted a prospective, observational study that assessed MBL concentration as a risk factor for infection in patients with hematological malignancy who were hospitalized to undergo at least 1 chemotherapy cycle. MBL deficiency was defined using an algorithm that considered the serum MBL concentration and the MBL genotype. The primary end point was the ratio of duration of febrile neutropenia to the duration of neutropenia. Secondary end points included the incidence of severe infection (e.g., sepsis, pneumonia, bacteremia, and invasive fungal infection). Logistic regression analysis was conducted, and Fisher's exact test was used to analyze binary outcomes, and Kaplan-Meier estimates and log rank tests were used for time-to-event variables. RESULTS: We analyzed 255 patients who received 569 cycles of chemotherapy. The median duration of neutropenia per cycle was 7 days (interquartile range, 0-13 days). Sixty-two patients (24%) were found to have MBL deficiency. Febrile neutropenia occurred at least once in 200 patients. No difference in the primary outcome was seen. The incidence of severe infection was higher among MBL-deficient patients than among non-MBL-deficient patients (1.96 vs. 1.34 cases per 100 days for analysis of all patients [P=.008] and 1.85 vs. 0.94 cases per 100 days excluding patients with acute leukemia [P<.001]). CONCLUSIONS: MBL deficiency does not predispose adults with hematological cancer to more-frequent or more-prolonged febrile episodes during myelosuppressive chemotherapy, but MBL-deficient patients have a greater number of severe infections and experience their first severe infection earlier, compared with nondeficient patients.

Factors that influence cancer patients' anxiety following a medical consultation: impact of a communication skills training programme for physicians.

BACKGROUND: No study has yet assessed the impact of physicians' skills acquisition after a communication skills training programme on the evolution of patients' anxiety following a medical consultation. This study aimed to compare the impact, on patients' anxiety, of a basic communication skills training programme (BT) and the same programme consolidated by consolidation workshops (CW), and to investigate physicians' communication variables associated with patients' anxiety. PATIENTS AND METHODS: Physicians, after attending the BT, were randomly assigned to CW or to a waiting list. The control group was not a non-intervention group. Consultations with a cancer patient were recorded. Patients' anxiety was assessed with the State Trait Anxiety Inventory before and after a consultation. Communication skills were analysed according to the Cancer Research Campaign Workshop Evaluation Manual. RESULTS: No statistically significant change over time and between groups was observed. Mixed-effects modelling showed that a decrease in patients' anxiety was linked with screening questions (P = 0.045), physicians' satisfaction about support given (P = 0.004) and with patients' distress (P < 0.001). An increase in anxiety was linked with breaking bad news (P = 0.050) and with supportive skills (P = 0.013). No impact of the training programme was observed. CONCLUSIONS: This study shows the influence of some communication skills on the evolution of patients' anxiety. Physicians should be aware of these influences.

Can we predict the duration of chemotherapy-induced neutropenia in febrile neutropenic patients, focusing on regimen-specific risk factors? A retrospective analysis.

BACKGROUND: The aim of the study was to elaborate a predictive model for the duration of chemotherapy-induced neutropenia (CIN) allowing the identification of patients with a higher risk of complications, especially complicated febrile neutropenia, who might benefit from preventive measures. PATIENTS AND METHODS: A score ranging from 0 to 4 on the basis of expected CIN was attributed to each cytotoxic agent given as part of chemotherapy treatment in solid tumours for patients with febrile neutropenia (FN). The individual scores were combined into several overall scores. RESULTS: A total of 203 patients with FN were eligible for this retrospective analysis. We were able to identify two groups of patients with statistically different neutropenia durations with median durations until hematological recovery of ANC > or =0.5 and > or =1.0 x 10(9)/l, being respectively 6 versus 4 days (P = 0.03) and 8 versus 6 days (P = 0.01). CONCLUSIONS: The duration of neutropenia is directly influenced by the aggressiveness of the chemotherapy regimen. In this retrospective study, we were able to identify a group of patients who needed two more additional days to recover from grade 3 and grade 4 neutropenia, based on the degree of aggressiveness of the cytotoxic agents used.

[New trends in the management of common solid malignant tumors]. / Tendances nouvelles dans le traitement des tumeurs solides malignes les plus fréquentes.

Evidence-based medicine has become a requisite for novel therapies. It requires demonstration, in well performed clinical trials, that a benefit for the patients can be obtained by changing what is considered as a standard treatment. The present review deals with the clinical trials in the field of cancer therapy which have been published, during 2004, mainly in the New England Journal of Medicine (NEJM). We selected this mode of operation since the NEJM publishes highly selected papers after thoroughful peer review; moreover, the selection of the paper published by the NEJM is intended for general practionners in the different areas of medicine and critical editorial comments are offered for major contributions.

Ovarian cancer: state of the art and future directions.

The median survival of patients with ovarian cancer has increased steadily, mainly due to a multidisciplinary approach including surgery and chemotherapy. This editorial article summarizes the important messages taken from clinical research performed in this field over the last 15 years. It deals with the following issues: screening, prevention, management of early and advanced disease, maintenance/consolidation therapies and the treatment of relapsing patients. It also gives some future directions with the hope to improve the management and the outcome of this highly lethal disease.

A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear. PATIENTS AND METHODS: We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC). RESULTS: Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups. CONCLUSION: The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required.

Prolonged schedule of temozolomide (Temodal) plus liposomal doxorubicin (Caelyx) in advanced solid cancers.

Temozolomide (Temodal) is an oral imidazotetrazine. Increased temozolomide exposure and subsequent depletion of O-alkylguanine alkyltransferase may improve the activity of temozolomide. The rationale for investigating temozolomide plus Caelyx is based on their antitumor activity, their formulation and no significant overlapping toxicities. We conducted a study of a prolonged schedule of temozolomide (orally on days 1-7 and 15-21) plus Caelyx (day 1) every 28 days. Twenty-one patients (melanoma n=10, sarcoma n=7 and other n=4) were assigned to four dose levels (DL; temozolomide+Caelyx, mg/m): DL1: 100+30 (n=3 patients), DL2: 100+40 (n=6 patients), DL3: 125+40 (n=6 patients) and DL4: 150+40 (n=6 patients). Dose-limiting toxicities were noted after 2 or more cycles in one patient at DL3 (stomatitis) and one patient at DL4 (grade 4 ANC >/=7 days). Treatment delays and/or dose reductions (due to hematological toxicity) were necessary in five of six patients receiving DL4 compared with one of six patients at DL3, and one patient at DL1 and 2. Thus, the recommended dose was temozolomide 125 mg/m (daily for 7 days every other week) plus Caelyx 40 mg/m (day 1 every 4 weeks). Other toxicities were mild. Antitumor activity was observed in eight patients, including one complete response (melanoma), three partial responses (one melanoma, two sarcomas) and four patients with stable disease (three melanomas, one Ewing), with a duration lasting from 14 to 135+weeks. Two melanoma patients showed tumor stabilization in non-irradiated cerebral lesions. This schedule of temozolomide allowed higher dose intensity (1750 mg/m in 4 weeks) compared to the standard 5-day regimen (1000 mg/m in the same amount of time).