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.

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

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.

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.

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.

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.

Late intensification in small-cell lung cancer: a phase I study of high doses of cyclophosphamide and etoposide with autologous bone marrow transplantation.

We conducted a late dose intensification pilot study of small-cell lung cancer (SCLC) treated with high doses of cyclophosphamide (200 mg/kg) and etoposide (1.0 to 3.5 g/m2), administered during a period of 48 hours, as well as autologous bone marrow infusion. We have been able to administer safely 3 g/m2 of etoposide with the autologous bone marrow infusion and 1.5 g/m2 without it. Limiting extrahematopoietic toxicity appeared to take the form of irreversible cardiac failure. Complete responses have been obtained with our regimen for late dose intensification, but the duration of the responses and the survival rates of the patients were poor. This suggests that late dose intensification in incomplete responders is not superior to the usually reported results obtained with standard regimens for the treatment of SCLC.

A randomized study comparing cisplatin or carboplatin with etoposide in patients with advanced non-small-cell lung cancer: European Organization for Research and Treatment of Cancer Protocol 07861.

The European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Working Party conducted a randomized trial comparing cisplatin (CDDP; 120 mg/m2, day 1) and carboplatin (CBDCA; 325 mg/m2, day 1) in combination with etoposide (VP16; 100 mg/m2, days 1, 2, and 3) in advanced non-small-cell lung cancer (NSCLC). Two hundred twenty-eight patients were eligible for survival and 202 assessable for response. We obtained 27 of 100 objective responses (ORs; 27%) in the CDDP arm and 16 of 102 (16%) in the CBDCA arm (P = .07). There was no significant difference in survival. Toxicity, consisting mainly of myelosuppression and renal function impairment, was significantly increased in the patients receiving the CDDP treatment. We conclude that CDDP plus VP16 was more active but also more toxic than CBDCA plus VP16 in advanced NSCLC.

A randomized study comparing a high and a standard dose of cisplatin in combination with etoposide in the treatment of advanced non-small-cell lung carcinoma.

We conducted a randomized trial comparing a high (120 mg/m2 day 1) v a standard (60 mg/m2 day 1) dose of cisplatin in combination with etoposide (120 mg/m2 days 3, 5, and 7) in advanced non-small-cell lung carcinoma (NSCLC). Two hundred forty-one patients were evaluable for survival and 207 for response. We obtained a 25% objective response rate in the standard-dose arm and 29% in the high-dose arm; this difference was not statistically significant. There was no significant improvement in the overall survival or survival of responders with the high-dose regimen. However, toxicity (mainly myelosuppression) was significantly increased in the patients receiving the higher dose of cisplatin. An analysis of prognostic factors showed that disease progression, loss of body weight, performance status, and prior therapy were predictive parameters of survival.

Cisplatin versus cisplatin plus etoposide in the treatment of advanced non-small-cell lung cancer. Lung Cancer Working Party, Belgium.

We conducted a randomized study comparing the survival after treatment with cisplatin (120 mg/m2) or cisplatin plus etoposide (100 mg/m2 on days 1, 2, and 3) in 162 evaluable patients with advanced non-small-cell lung cancer (NSCLC). No statistically significant difference in survival was detected; the median survival was 26 and 22 weeks, respectively, for patients receiving cisplatin and for those receiving cisplatin plus etoposide. The objective response rate was 19% for cisplatin and 26% for the combination; the corresponding response rates were 17% and 43% in patients with limited disease. No significant differences were detected between the two study arms as far as toxicity was concerned, except for alopecia and granulocytopenia, which occurred more frequently in patients treated with cisplatin plus etoposide.

Phase II randomized trial comparing high-dose cisplatin with moderate-dose cisplatin and carboplatin in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE: A phase II randomized trial was conducted in patients with advanced non-small-cell lung cancer (NSCLC) to determine if the combination of moderate-dose cisplatin and carboplatin was active (primary end point) and could avoid the long-term limiting (renal, auditive, neurologic) toxicity of high-dose cisplatin, which prevents prolonged administration (secondary end point). PATIENTS AND METHODS: One hundred twenty-one patients, registered between April 1990 and September 1991, were randomized to receive high-dose cisplatin (120 mg/m2 intravenously [IV] on day 1) or a combination of moderate-dose carboplatin (200 mg/m2 IV on day 1 and moderate-dose cisplatin (30 mg/m2 IV on days 2 and 3). One hundred nine patients were eligible: 56 in the cisplatin arm and 53 in the combined arm; 52 and 47, respectively, were assessable for response. All had stage IV disease (or stage IIIB with pleural effusion) and none had received prior chemotherapy. RESULTS: There was a 23% objective response rate to cisplatin (23% of the eligible patients) and a 22% response rate to cisplatin plus carboplatin (21% of the eligible patients). The overall survival rate was not significantly different between the two study arms, but responders in the combined arm survived significantly longer than those in the high-dose cisplatin arm (respective median survival durations, 66 and 30 weeks). Although there was no difference between the arms for alopecia, emesis, and leukopenia, the combined arm was significantly associated with more thrombocytopenia (although rarely severe) and, more importantly, with less renal (19% v 36%), auditive (4% v 16%), and neurologic (0% v 16%) toxicity of any grade. CONCLUSION: The regimen combining moderate-dose cisplatin and carboplatin was active against advanced NSCLC and significantly less toxic than high-dose cisplatin.

The Multinational Association for Supportive Care in Cancer risk index: A multinational scoring system for identifying low-risk febrile neutropenic cancer patients.

PURPOSE: Febrile neutropenia remains a potentially life-threatening complication of anticancer chemotherapy, but some patients are at low risk for serious medical complications. The purpose of this study was to develop an internationally validated scoring system to identify these patients. MATERIALS AND METHODS: Febrile neutropenic cancer patients were observed in a prospective multinational study. Independent factors assessable at fever onset, predicting low risk of complications, on a randomly selected derivation set, were assigned integer weights to develop a risk-index score, which was subsequently tested on a validation set. RESULTS: On the derivation set (756 patients), predictive factors were a burden of illness indicating absence of symptoms or mild symptoms (weight, 5; odds ratio [OR], 8.21; 95% confidence interval [CI], 4.15 to 16.38) or moderate symptoms (weight, 3; OR, 3.70; 95% CI, 2.18 to 6.29); absence of hypotension (weight, 5; OR, 7.62; 95% CI, 2.91 to 19.89); absence of chronic obstructive pulmonary disease (weight, 4; OR, 5. 35; 95% CI, 1.86 to 15.46); presence of solid tumor or absence of previous fungal infection in patients with hematologic malignancies (weight, 4; OR, 5.07; 95% CI, 1.97 to 12.95); outpatient status (weight, 3; OR, 3.51; 95% CI, 2.02 to 6.04); absence of dehydration (weight, 3; OR, 3.81; 95% CI, 1.89 to 7.73); and age less than 60 years (weight, 2; OR, 2.45; 95% CI, 1.51 to 4.01). On the validation set, a Multinational Association for Supportive Care in Cancer risk-index score >/= 21 identified low-risk patients with a positive predictive value of 91%, specificity of 68%, and sensitivity of 71%. CONCLUSION: The risk index accurately identifies patients at low risk for complications and may be used to select patients for testing therapeutic strategies that may be more convenient or cost-effective.

Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE AND METHODS: The European Lung Cancer Working Party (ELCWP) performed a randomized trial with the primary end point to determine if maintenance chemotherapy with 12 courses of etoposide (120 mg/m2 on days 1 and 3) and vindesine (3 mg/m2 on day 3) could improve progression-free survival in small-cell lung cancer (SCLC) patients who responded to six courses of induction chemotherapy with ifosfamide, etoposide, and an anthracycline (doxorubicin or epirubicin). RESULTS: Among 235 eligible patients initially registered, 91 were randomized to receive maintenance therapy, including seven patients who were no longer responding. Among 84 randomized responders, progression-free survival was significantly improved (P = .003) by maintenance therapy, with median durations (maintenance v follow-up) of 25 versus 12 weeks after the second randomization, but survival was not significantly increased (P = .10), with median durations of 48 and 38 weeks. However, in a multi-variate analysis that took into account disease extent, maintenance therapy, Karnofsky performance status (PS), and absolute dose-intensity (ADI) of anthracycline given during induction, limited disease (LD) and maintenance were found to be independent positive predictors of survival. CONCLUSION: We conclude that maintenance chemotherapy in responding patients is beneficial in SCLC.

Phase III randomized trial comparing cisplatin and carboplatin with or without ifosfamide in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE: A phase III randomized trial in patients with advanced non-small-cell lung cancer (NSCLC) was performed to determine if the addition of ifosfamide to moderate-dose cisplatin and carboplatin improved response rate (primary end point) and survival. PATIENTS AND METHODS: A total of 529 patients were randomized to receive a combination of moderate-dose carboplatin (200 mg/m2 intravenously [i.v.] on day 1) and cisplatin (30 mg/m2 i.v. on days 2 and 3) with (CCI arm) or without (CC arm) ifosfamide (1.5 g/m2 i.v. on days 1 to 3). There were 248 eligible patients on the CC arm and 257 on the CCI arm, with 220 and 238 patients assessable for response, respectively. All but 23 had stage IV disease with pleural effusion. RESULTS: There was a 16% objective response (OR) rate to CC and a 31% OR rate to CCI. That observed difference was highly statistically significant (P < 0.001). Duration of response and survival were not statistically different between arms. The CCI regimen was associated with significantly more acute toxicities: emesis, alopecia, leukopenia, and thrombocytopenia. The frequency of chronic renal, auditive, and peripheral neurologic toxicity was low in both arms (4.6% and 6.6%, respectively, after six courses of chemotherapy). The relative dose-intensity (RDI) of the CCI arm was significantly lower than that of the CC arm. CONCLUSION: The addition of ifosfamide to moderate-dose cisplatin and carboplatin significantly improves the antitumoral response rate, but has no apparent effect an survival in advanced NSCLC.

Treatment of severe infections in patients with cancer. The role of new acyl-penicillins.

At the present time, gram-negative bacillary bacteremia in patients with neutropenia will respond favorably in 60% to 70% of the patients when carbenicillin-ticarcillin or cephalothin-cefazolin combined with aminoglycosides (gentamicin, tobramycin, sisomicin, netilmicin, or amikacin) are given. Piperacillin alone will cure 20/34 (59%) of bacteremic episodes in patients without granulocytopenia who have a severe underlying disease. In patients with neutropenia, the combination of piperacillin with amikacin was found to be associated with a favorable response in 76/121 patients (63%). These results are thus as good as those obtained with other broad-spectrum, beta-lactam antibiotics whether used alone in patients without granulocytopenia or in combination with aminoglycosides in patients with neutropenia. It seems likely that in patients with severe underlying disease and/or granulocytopenia, antibiotic combinations have reached an optimal efficacy. More attention should be paid to the correction of the basic predisposing factors to infection (granulocytopenia and immunodepression) and to infections caused by nonbacterial pathogens.