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Papers by John Hanson

Clinical breast cancer, Jan 25, 2015

Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in sing... more Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in single nucleotide polymorphisms (SNPs). We studied whether the -161 C > T germline SNP in UGT2B7 was related to epirubicin metabolism and whether differences exist in the toxicity and efficacy of epirubicin-based chemotherapy among patients who were TT homozygotes, CT heterozygotes, and CC homozygotes. A total of 132 women with non-metastatic breast cancer receiving FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)) were prospectively enrolled. Toxicity was assessed in cycle 1 using the National Cancer Institute Common Toxicity Criteria, version 2.0. The sequence at -161 was studied in 132 subjects; 37 were TT homozygotes, 63 were CT heterozygotes, 26 were CC homozygotes, and 6 could not be genotyped. The CC genotype patients had decreased epirubicin clearance (median, 103.3 L/hr) compared with the CT/TT genotype patients (median, 134.0 L/hr; P = .002)....

Cancer biology & therapy, Jan 10, 2015

Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is... more Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines...

Astrodynamics Conference, 1990

Design of satellite constellations providing partial coverage of certain ground regions is becomi... more Design of satellite constellations providing partial coverage of certain ground regions is becoming more important as small low-attitude satellites receive increased attention. The purpose of this study is to develop the procedures necessary for deriving the best constellations for partial coverage. This paper analyzes circular orbit constellations and shows that repeating ground-track orbits yield beter results than nonrepeating ground track

Radiotherapy and Oncology, 2010

To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurr... more To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurrent chemotherapy for limited-stage small cell lung cancer. Limited-stage small cell lung cancer patients were prescribed 54, 58, 62 or 65 Gy, all given in 25 daily fractions and commenced on or before the second chemotherapy cycle. Dose level accrual was performed sequentially. Conformal radiotherapy techniques were used and targeted gross disease plus margin. Four cycles of platinum-based chemotherapy were prescribed. Primary endpoint was the rate of acute RT toxicities according to NCI Common Toxicity Criteria scales. The dose which caused unacceptable acute radiotherapy toxicity rates according to pre-defined stopping rules defined the maximal tolerated radiotherapy dose. Six patients were accrued to each of the 54, 58 and 62 Gy dose levels. There were no radiotherapy-related deaths. No grade 3 toxicities occurred in the 54 and 58 Gy groups. There were 2 grade 3 RT toxicities in the 62 Gy group. There were 14 complete responses. Trial accrual has stopped at the 62 Gy group according to trial stopping rules. The maximal tolerated hypofractionated thoracic radiotherapy dose in this trial was 58 Gy in 25 daily fractions.

Radiotherapy and Oncology, 2012

To define the rate of development of symptomatic chest failures in extensive stage small cell lun... more To define the rate of development of symptomatic chest failures in extensive stage small cell lung cancer (ES-SCLC) after undergoing post-chemotherapy chest radiotherapy (RT). Patients had ES-SCLC, attained an objective response to chemotherapy and signed study consent. Target accrual was 33 patients. Patients were offered prophylactic cranial irradiation (PCI) as per department policy. PCI (25 Gy/10 fractions) and chest RT (40 Gy/15 fractions) were given simultaneously 4-8 weeks after chemotherapy completion. Thoracic target volume was the post-chemotherapy residual chest disease plus margin. Patients were evaluated for RT toxicities, local control, disease-free and overall survival. Thirty-two patients were evaluable. Twenty-nine patients completed RT without delay. There were 4 complete responses and 28 partial responses to chemotherapy. All study patients received PCI. Maximal acute RT toxicity was grade 2 esophagitis (18 patients). There were no RT-related deaths. Median time to disease progression and overall survival were 4.2 and 8.3 months, respectively (median follow-up=21.8 months). Of 16 chest recurrences, 7 were in the irradiated region and 5 were symptomatic. Post-chemotherapy consolidation chest RT for ES-SCLC patients on this trial was well tolerated and associated with symptomatic chest recurrences in only 5/32 treated patients.

PAIN, 1997

Morphine (M) and hydromorphone (HM) are commonly used opioid analgesics for cancer pain. Opioid r... more Morphine (M) and hydromorphone (HM) are commonly used opioid analgesics for cancer pain. Opioid rotation is often necessary in the event of toxicity and/or inadequate analgesia. Equianalgesic reference tables based on single dose comparisons are possibly inadequate for patients on chronic treatment and developing tolerance. This retrospective study of opioid rotation involving M and HM sought to determine the equianalgesic dose ratio for 91 rotations in 74 consecutively evaluable cancer pain patients. Only rotations involving subcutaneous (s.c.-s.c.) and oral (p.o.-p.o.) routes were evaluated. There were 44 rotations from M-HM (34: s.c.-s.c., 10: p.o.-p.o.) and 47 rotations from HM-M (35: s.c.-s.c., 12: p.o.-p.o.). Expressing all ratios as M/HM, the median dose ratios (lower-upper quartiles) for s.c. and p.o. rotations were 4.92 (4.1-5.9) vs. 5.76 (4.9-5.8) for M-HM (P = 0.28, NS) and 4.0 (3.1-4.8) vs. 3.45 (2.8-4.2) for HM-M (P = 0.4, NS), respectively. Pain intensity, as measured on a visual analogue scale (VASP), showed no significant difference between mean values pre- and post-rotation. A unified overall median dose ratio of 4.29 (3.3-5.3, lower-upper quartiles) was calculated by expressing all of the HM-M dose ratios as M/HM and combining them with the dose ratios for all of the M-HM rotations. This suggests a potency ratio of approximately 4.3:1 between M and HM. When expressed as M/HM for dose ratio comparison, the median dose ratio for all HM-M rotations was 3.7 (2.9-4.5, lower-upper quartiles) vs. 5 (4.2-5.9) for M-HM rotations (P = 0.0001), suggesting that the opioid to which rotation is taking place is more potent than our proposed unified overall median dose ratio of 4.29:1 would predict. Our data suggests that HM is 5 times more potent than M when given second (M-HM), but is only 3.7 times more potent when given first (HM-M). We therefore recommend a ratio of 5 for M/HM in rotating from M to HM and ratio of 3.7 for M/HM when rotating from HM to M in patients exposed to chronic dosing of these opioids. There was no correlation observed between M-HM and HM-M dose ratios and the level of previous opioid dose, in contrast to HM to methadone rotation where the dose ratio was higher in patients receiving higher doses of HM.

Journal of Pain and Symptom Management, 2000

A 9-item mail survey dealing with availability and characteristics of undergraduate medical educa... more A 9-item mail survey dealing with availability and characteristics of undergraduate medical education programs in palliative medicine was sent to all medical schools in Canada and the United Kingdom (UK) (30), and 129 randomly selected medical schools in the United States (US) and Western Europe. The overall response rate was 117/175 (67%). The highest percentage of mandatory (required by the university) rotations in palliative medicine was in the UK medical schools (14/22, 64%). Considerably lower numbers were obtained from the other countries: US; 4/37, 11%, Canada; 2/14, 14%, and Western Europe; 8/43, 19% ( P ϭ 0.001). Elective rotations in palliative medicine were more readily available in the UK; 18/22, 82% and Canada; 10/14, 71%, compared with the US; 23/37, 62%, and Western Europe; 13/43, 30% ( P ϭ 0.001). Seventy-two percent (13/18) of UK, 70% (7/10) of Canadian, 59% (16/27) of US, and 9/30 (30%) of Western European medical schools provide educational reading material in palliative medicine ( P ϭ 0.014). Case-based learning in small groups and small group discussion were favored by the UK, 14/22 (63%) and 17/22 (77%), respectively, and Canadian medical schools, 8/14 (57%) and 8/14 (57%), respectively ( P ϭ . The number of universities with academic faculty positions for palliative medicine and the median number of positions for the countries were as follows-Canada 8/13 (62%) and 2; UK 12/22 (55%) and 1; US 5/36 (14%) and 1; and Western Europe 9/24 (21%) and 1, respectively ( P ϭ 0.001). Besides the UK, mandatory (required) rotations in undergraduate palliative medicine education are lacking in Canadian, US, and Western European medical schools. The median number of 1 academic faculty member per responding medical school is discouraging. In order for undergraduate and postgraduate medical education in palliative medicine to improve, the number of both educational programs and faculty members will need to be increased.

Journal of Pain and Symptom Management, 1995

The purpose of this retrospective study was to determine the prevalence of alcoholism among termi... more The purpose of this retrospective study was to determine the prevalence of alcoholism among terminally ill cancer patients when assessed by multidisciplinary interviews and by the CAGE Questionnaire. We reviewed the charts of 100 consecutive patients assessed by a multidisciplinary team for the presence of alcoholism during 1989, and 100 consecutive patients assessed by the CAGE Questionnaire during 1992. Alcoholism was diagnosed in 28/100 patients during 1989 (28%) and 18/66 patients during 1992 (27%). Thirty-four patients were unable to complete the CAGE Questionnaire in 1992 because of sedation or cognitive impairment; six of these patients (17%) were found to be alcoholics after multidisciplinary assessment. Only 9/28 (32%) and 8/24 (33%) patients diagnosed as alcoholics during 1989 and 1992, respectively, had been previously diagnosed as alcoholics according to the medical charts. The mean equivalent daily dose of morphine during admission and on Day 2 during 1992 were 153 +/- 193 mg and 183 +/- 198 for alcoholic patients, versus 58 +/- 80 and 70 +/- 79 mg for nonalcoholics (P = 0.06 and 0.03, respectively). The maximal dose of opioid and the pain intensity during admission, however, were not significantly different between alcoholics and nonalcoholics. Our results suggest that alcoholism is highly prevalent and underdiagnosed among symptomatic terminally ill cancer patients. The CAGE Questionnaire should be used for screening for alcoholism in this population. When multidimensional assessment and management of pain is applied, the outcome of alcoholic patients appears to be similar to that of nonalcoholics.

Journal of Pain and Symptom Management, 2003

This trial compared pain, quality of life, and analgesic use in a sample of patients with cancer ... more This trial compared pain, quality of life, and analgesic use in a sample of patients with cancer pain (n ϭ 24) who received either standard opioid management plus rest (Arm A) or standard opioid management plus Reiki (Arm B). Participants either rested for 1.5 hr on Days 1 and 4 or received two Reiki treatments (Days 1 and 4) one hour after their first afternoon analgesic dose. Visual analogue scale (VAS) pain ratings, blood pressure, heart rate, and respirations were obtained before and after each treatment/rest period. Analgesic use and VAS pain scores were reported for 7 days. Quality of life was assessed on Days 1 and 7. Participants in Arm B experienced improved pain control on Days 1 and 4 following treatment, compared to Arm A, and improved quality of life, but no overall reduction in opioid use. Future research will determine the extent to which the benefits attributed to Reiki in this study may have been due to touch. J Pain Symptom Manage 2003;26:990-997. Ć 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Journal of Pain and Symptom Management, 1995

Two hundred and seventy-seven patients were admitted to this prospective multicenter study in ord... more Two hundred and seventy-seven patients were admitted to this prospective multicenter study in order to assess the accuracy of a staging system for cancer pain. The staging system (SS) was completed by a trained physician during the initial consultation. This system included the assessment of pain mechanism (PM, neuropathic versus nonneuropathic), pain characteristic (PC, continuous versus incidental), previous opioid dose (OD), cognitive function (CF), psychological distress (PD), tolerance (T), past history of alcohol or drugs (A). During day 21, a final assessment of pain control was made. Agreement for staging was observed in 96% of cases for investigators 1 and 2 (kappa 0.76, P < 0.001), and in 84% of cases between investigators 1 and 3 (kappa 0.723, P < 0.001). Of 276 evaluable patients, 86/92 Stage I (good prognosis) patients achieved good PC (93%) versus 102/184 Stage II and III (poor prognosis) patients (55%, P < 0.001). Sensitivity and specificity of the system were found to be 0.93 and 0.46, respectively. Univariate correlation found significant correlation between pain control and all variables except CF. In logistic regression, CF and OD showed no significant correlation. We, therefore, propose a more simple SS of five categories (PM, PC, PD, T, and A) and two stages (good and poor prognosis). We conclude that the SS is highly accurate in predicting patients with good prognosis, but patients with "poor prognosis" can still achieve good pain control in more than 50% of cases.

Journal of Pain and Symptom Management, 2011

... Robin Fainsinger, MD; Odette Spruyt, MBChB, FRACP, FRAChPM; Lyle Galloway, MD CCFP; Michael F... more ... Robin Fainsinger, MD; Odette Spruyt, MBChB, FRACP, FRAChPM; Lyle Galloway, MD CCFP; Michael Fisch, MD MPH; Gina Kaye, MbChb MRCP(UK) MRNZCGP; John Hanson; Eduardo Bruera, MD; Donna Zhukovsky, MD FACP FAAHPM; Willem Landman, MBChB FAChPM ...

European Journal of Cancer, 2010

European Journal of Anaesthesiology, 2006

The purpose of this randomized, double-blind study was to compare 300 units of hyaluronidase per ... more The purpose of this randomized, double-blind study was to compare 300 units of hyaluronidase per one-half liter to 150 units per one-half liter in patients receiving brief infusions for subcutaneous hydration. Twenty-five evaluable patients were randomized to receive a local injection of 300 units of hyaluronidase or 150 units of hyaluronidase immediately before two 1-hr infusions of two-thirds dextrose 5% and one-third normal saline solution (500 cc volume). The following day a crossover took place, and patients received the alternate treatment before each of the two 1-hr infusions. The intensity and swelling as reported by the patient (visual analogue scale 0-100), and the intensity of edema and rash as assessed by the investigator (score 0-4) were not significantly different between groups. The patients' and investigators' final choice was also not significantly different. Patients could not distinguish between bolus and their previous experience with overnight clysis. Our results suggest that brief infusions are well tolerated for subcutaneous hydration of patients with advanced cancer. A concentration of 150 units of hyaluronidase per one-half liter is well tolerated in this population.

Cancer, 2007

BACKGROUND. The authors investigated how lymphopenia and low serum albumin levels correlate with ... more BACKGROUND. The authors investigated how lymphopenia and low serum albumin levels correlate with the prognosis of patients with carcinoma of unknown primary (CUP).

Breast Cancer Research and Treatment, 2010

We investigated the association between the risk of locoregional recurrence (LRR) and biological ... more We investigated the association between the risk of locoregional recurrence (LRR) and biological subtypes defined by hormonal receptors (HR) and HER-2 status in women with invasive breast cancer (BC). A total of 618 newly diagnosed BC patients were identified from a cancer registry within a single institution with standardized methods of tumor assessment for estrogen receptor (ER), progesterone receptor (PR), and HER-2. Patients were stratified based on surgical treatment, breast-conserving therapy (BCT) versus modified radical mastectomy (MRM), as well as biological subtypes: HR+/HER-2- (ER-positive or PR-positive, HER-2-negative), HR+/HER-2+ (ER-positive or PR-positive, HER-2-positive), HR-/HER-2+ (ER-negative and PR-negative, HER-2-positive) and TN (ER-negative, PR-negative and HER-2-negative). The association between clinicopathological factors, biological subtype and LRR was evaluated with univariate and multivariate Cox analysis. With a median follow-up of 4.8 years, the rate of LRR was 7.5%. On multivariate analysis, TN, tumor size ≥2 cm and lymph node (LN) positivity were associated with increased risk of LRR (P = 0.023, P = 0.048, and P = 0.0034, respectively). In BCT group, HR-/HER-2+ and LN positivity were associated with increased risk of LRR (HR 11.13; 95% CI 2.78-44.53; P = 0.0007 and HR 5.40; 95% CI 1.67-17.43; P = 0.0048, respectively). In MRM group, TN subtype and LN positivity were associated with increased risk of LRR (HR 4.72; 95% CI 1.53-14.52; P = 0.0069 and HR 3.23; 95% CI 1.44-7.29; P = 0.0047, respectively). Compared to HR+/HER-2-, HR-/HER-2+ treated by BCT and TN treated by MRM showed a significant decrease of 5-year LRR free survival (P = 0.0002 and P = 0.002, respectively). Tumor profiling using ER, PR, and HER-2 biomarkers is a promising tool to identify patients at high risk of LRR based on surgical treatment. Our findings suggest a different follow-up and locoregional treatment for patients with HR-/HER-2+ and TN subtypes.

Clinical breast cancer, Jan 25, 2015

Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in sing... more Epirubicin is metabolized by uridine glucuronosyltransferase 2B7 (UGT2B7), an enzyme rich in single nucleotide polymorphisms (SNPs). We studied whether the -161 C > T germline SNP in UGT2B7 was related to epirubicin metabolism and whether differences exist in the toxicity and efficacy of epirubicin-based chemotherapy among patients who were TT homozygotes, CT heterozygotes, and CC homozygotes. A total of 132 women with non-metastatic breast cancer receiving FEC (5-fluorouracil 500 mg/m(2), epirubicin 100 mg/m(2), cyclophosphamide 500 mg/m(2)) were prospectively enrolled. Toxicity was assessed in cycle 1 using the National Cancer Institute Common Toxicity Criteria, version 2.0. The sequence at -161 was studied in 132 subjects; 37 were TT homozygotes, 63 were CT heterozygotes, 26 were CC homozygotes, and 6 could not be genotyped. The CC genotype patients had decreased epirubicin clearance (median, 103.3 L/hr) compared with the CT/TT genotype patients (median, 134.0 L/hr; P = .002)....

Cancer biology & therapy, Jan 10, 2015

Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is... more Radiation therapy (RT) the front-line treatment after surgery for early breast cancer patients is associated with acute skin toxicities in at least 40% of treated patients. Monocyte-derived macrophages are polarized into functionally distinct (M1 or M2) activated phenotypes at injury sites by specific systemic cytokines known to play a key role in the transition between damage and repair in irradiated tissues. The role of M1 and M2 macrophages in RT-induced acute skin toxicities remains to be defined. We investigated the potential value of M1 and M2 macrophages as predictive factors of RT-induced skin toxicities in early breast cancer patients treated with adjuvant RT after lumpectomy. Blood samples collected from patients enrolled in a prospective clinical study (n = 49) were analyzed at baseline and after the first delivered 2Gy RT dose. We designed an ex vivo culture system to differentiate patient blood monocytes into macrophages and treated them with M1 or M2-inducing cytokines...

Astrodynamics Conference, 1990

Design of satellite constellations providing partial coverage of certain ground regions is becomi... more Design of satellite constellations providing partial coverage of certain ground regions is becoming more important as small low-attitude satellites receive increased attention. The purpose of this study is to develop the procedures necessary for deriving the best constellations for partial coverage. This paper analyzes circular orbit constellations and shows that repeating ground-track orbits yield beter results than nonrepeating ground track

Radiotherapy and Oncology, 2010

To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurr... more To define the maximal tolerated dose of hypofractionated thoracic radiotherapy given with concurrent chemotherapy for limited-stage small cell lung cancer. Limited-stage small cell lung cancer patients were prescribed 54, 58, 62 or 65 Gy, all given in 25 daily fractions and commenced on or before the second chemotherapy cycle. Dose level accrual was performed sequentially. Conformal radiotherapy techniques were used and targeted gross disease plus margin. Four cycles of platinum-based chemotherapy were prescribed. Primary endpoint was the rate of acute RT toxicities according to NCI Common Toxicity Criteria scales. The dose which caused unacceptable acute radiotherapy toxicity rates according to pre-defined stopping rules defined the maximal tolerated radiotherapy dose. Six patients were accrued to each of the 54, 58 and 62 Gy dose levels. There were no radiotherapy-related deaths. No grade 3 toxicities occurred in the 54 and 58 Gy groups. There were 2 grade 3 RT toxicities in the 62 Gy group. There were 14 complete responses. Trial accrual has stopped at the 62 Gy group according to trial stopping rules. The maximal tolerated hypofractionated thoracic radiotherapy dose in this trial was 58 Gy in 25 daily fractions.

Radiotherapy and Oncology, 2012

To define the rate of development of symptomatic chest failures in extensive stage small cell lun... more To define the rate of development of symptomatic chest failures in extensive stage small cell lung cancer (ES-SCLC) after undergoing post-chemotherapy chest radiotherapy (RT). Patients had ES-SCLC, attained an objective response to chemotherapy and signed study consent. Target accrual was 33 patients. Patients were offered prophylactic cranial irradiation (PCI) as per department policy. PCI (25 Gy/10 fractions) and chest RT (40 Gy/15 fractions) were given simultaneously 4-8 weeks after chemotherapy completion. Thoracic target volume was the post-chemotherapy residual chest disease plus margin. Patients were evaluated for RT toxicities, local control, disease-free and overall survival. Thirty-two patients were evaluable. Twenty-nine patients completed RT without delay. There were 4 complete responses and 28 partial responses to chemotherapy. All study patients received PCI. Maximal acute RT toxicity was grade 2 esophagitis (18 patients). There were no RT-related deaths. Median time to disease progression and overall survival were 4.2 and 8.3 months, respectively (median follow-up=21.8 months). Of 16 chest recurrences, 7 were in the irradiated region and 5 were symptomatic. Post-chemotherapy consolidation chest RT for ES-SCLC patients on this trial was well tolerated and associated with symptomatic chest recurrences in only 5/32 treated patients.

PAIN, 1997

Morphine (M) and hydromorphone (HM) are commonly used opioid analgesics for cancer pain. Opioid r... more Morphine (M) and hydromorphone (HM) are commonly used opioid analgesics for cancer pain. Opioid rotation is often necessary in the event of toxicity and/or inadequate analgesia. Equianalgesic reference tables based on single dose comparisons are possibly inadequate for patients on chronic treatment and developing tolerance. This retrospective study of opioid rotation involving M and HM sought to determine the equianalgesic dose ratio for 91 rotations in 74 consecutively evaluable cancer pain patients. Only rotations involving subcutaneous (s.c.-s.c.) and oral (p.o.-p.o.) routes were evaluated. There were 44 rotations from M-HM (34: s.c.-s.c., 10: p.o.-p.o.) and 47 rotations from HM-M (35: s.c.-s.c., 12: p.o.-p.o.). Expressing all ratios as M/HM, the median dose ratios (lower-upper quartiles) for s.c. and p.o. rotations were 4.92 (4.1-5.9) vs. 5.76 (4.9-5.8) for M-HM (P = 0.28, NS) and 4.0 (3.1-4.8) vs. 3.45 (2.8-4.2) for HM-M (P = 0.4, NS), respectively. Pain intensity, as measured on a visual analogue scale (VASP), showed no significant difference between mean values pre- and post-rotation. A unified overall median dose ratio of 4.29 (3.3-5.3, lower-upper quartiles) was calculated by expressing all of the HM-M dose ratios as M/HM and combining them with the dose ratios for all of the M-HM rotations. This suggests a potency ratio of approximately 4.3:1 between M and HM. When expressed as M/HM for dose ratio comparison, the median dose ratio for all HM-M rotations was 3.7 (2.9-4.5, lower-upper quartiles) vs. 5 (4.2-5.9) for M-HM rotations (P = 0.0001), suggesting that the opioid to which rotation is taking place is more potent than our proposed unified overall median dose ratio of 4.29:1 would predict. Our data suggests that HM is 5 times more potent than M when given second (M-HM), but is only 3.7 times more potent when given first (HM-M). We therefore recommend a ratio of 5 for M/HM in rotating from M to HM and ratio of 3.7 for M/HM when rotating from HM to M in patients exposed to chronic dosing of these opioids. There was no correlation observed between M-HM and HM-M dose ratios and the level of previous opioid dose, in contrast to HM to methadone rotation where the dose ratio was higher in patients receiving higher doses of HM.

Journal of Pain and Symptom Management, 2000

A 9-item mail survey dealing with availability and characteristics of undergraduate medical educa... more A 9-item mail survey dealing with availability and characteristics of undergraduate medical education programs in palliative medicine was sent to all medical schools in Canada and the United Kingdom (UK) (30), and 129 randomly selected medical schools in the United States (US) and Western Europe. The overall response rate was 117/175 (67%). The highest percentage of mandatory (required by the university) rotations in palliative medicine was in the UK medical schools (14/22, 64%). Considerably lower numbers were obtained from the other countries: US; 4/37, 11%, Canada; 2/14, 14%, and Western Europe; 8/43, 19% ( P ϭ 0.001). Elective rotations in palliative medicine were more readily available in the UK; 18/22, 82% and Canada; 10/14, 71%, compared with the US; 23/37, 62%, and Western Europe; 13/43, 30% ( P ϭ 0.001). Seventy-two percent (13/18) of UK, 70% (7/10) of Canadian, 59% (16/27) of US, and 9/30 (30%) of Western European medical schools provide educational reading material in palliative medicine ( P ϭ 0.014). Case-based learning in small groups and small group discussion were favored by the UK, 14/22 (63%) and 17/22 (77%), respectively, and Canadian medical schools, 8/14 (57%) and 8/14 (57%), respectively ( P ϭ . The number of universities with academic faculty positions for palliative medicine and the median number of positions for the countries were as follows-Canada 8/13 (62%) and 2; UK 12/22 (55%) and 1; US 5/36 (14%) and 1; and Western Europe 9/24 (21%) and 1, respectively ( P ϭ 0.001). Besides the UK, mandatory (required) rotations in undergraduate palliative medicine education are lacking in Canadian, US, and Western European medical schools. The median number of 1 academic faculty member per responding medical school is discouraging. In order for undergraduate and postgraduate medical education in palliative medicine to improve, the number of both educational programs and faculty members will need to be increased.

Journal of Pain and Symptom Management, 1995

The purpose of this retrospective study was to determine the prevalence of alcoholism among termi... more The purpose of this retrospective study was to determine the prevalence of alcoholism among terminally ill cancer patients when assessed by multidisciplinary interviews and by the CAGE Questionnaire. We reviewed the charts of 100 consecutive patients assessed by a multidisciplinary team for the presence of alcoholism during 1989, and 100 consecutive patients assessed by the CAGE Questionnaire during 1992. Alcoholism was diagnosed in 28/100 patients during 1989 (28%) and 18/66 patients during 1992 (27%). Thirty-four patients were unable to complete the CAGE Questionnaire in 1992 because of sedation or cognitive impairment; six of these patients (17%) were found to be alcoholics after multidisciplinary assessment. Only 9/28 (32%) and 8/24 (33%) patients diagnosed as alcoholics during 1989 and 1992, respectively, had been previously diagnosed as alcoholics according to the medical charts. The mean equivalent daily dose of morphine during admission and on Day 2 during 1992 were 153 +/- 193 mg and 183 +/- 198 for alcoholic patients, versus 58 +/- 80 and 70 +/- 79 mg for nonalcoholics (P = 0.06 and 0.03, respectively). The maximal dose of opioid and the pain intensity during admission, however, were not significantly different between alcoholics and nonalcoholics. Our results suggest that alcoholism is highly prevalent and underdiagnosed among symptomatic terminally ill cancer patients. The CAGE Questionnaire should be used for screening for alcoholism in this population. When multidimensional assessment and management of pain is applied, the outcome of alcoholic patients appears to be similar to that of nonalcoholics.

Journal of Pain and Symptom Management, 2003

This trial compared pain, quality of life, and analgesic use in a sample of patients with cancer ... more This trial compared pain, quality of life, and analgesic use in a sample of patients with cancer pain (n ϭ 24) who received either standard opioid management plus rest (Arm A) or standard opioid management plus Reiki (Arm B). Participants either rested for 1.5 hr on Days 1 and 4 or received two Reiki treatments (Days 1 and 4) one hour after their first afternoon analgesic dose. Visual analogue scale (VAS) pain ratings, blood pressure, heart rate, and respirations were obtained before and after each treatment/rest period. Analgesic use and VAS pain scores were reported for 7 days. Quality of life was assessed on Days 1 and 7. Participants in Arm B experienced improved pain control on Days 1 and 4 following treatment, compared to Arm A, and improved quality of life, but no overall reduction in opioid use. Future research will determine the extent to which the benefits attributed to Reiki in this study may have been due to touch. J Pain Symptom Manage 2003;26:990-997. Ć 2003 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.

Journal of Pain and Symptom Management, 1995

Two hundred and seventy-seven patients were admitted to this prospective multicenter study in ord... more Two hundred and seventy-seven patients were admitted to this prospective multicenter study in order to assess the accuracy of a staging system for cancer pain. The staging system (SS) was completed by a trained physician during the initial consultation. This system included the assessment of pain mechanism (PM, neuropathic versus nonneuropathic), pain characteristic (PC, continuous versus incidental), previous opioid dose (OD), cognitive function (CF), psychological distress (PD), tolerance (T), past history of alcohol or drugs (A). During day 21, a final assessment of pain control was made. Agreement for staging was observed in 96% of cases for investigators 1 and 2 (kappa 0.76, P < 0.001), and in 84% of cases between investigators 1 and 3 (kappa 0.723, P < 0.001). Of 276 evaluable patients, 86/92 Stage I (good prognosis) patients achieved good PC (93%) versus 102/184 Stage II and III (poor prognosis) patients (55%, P < 0.001). Sensitivity and specificity of the system were found to be 0.93 and 0.46, respectively. Univariate correlation found significant correlation between pain control and all variables except CF. In logistic regression, CF and OD showed no significant correlation. We, therefore, propose a more simple SS of five categories (PM, PC, PD, T, and A) and two stages (good and poor prognosis). We conclude that the SS is highly accurate in predicting patients with good prognosis, but patients with "poor prognosis" can still achieve good pain control in more than 50% of cases.

Journal of Pain and Symptom Management, 2011

... Robin Fainsinger, MD; Odette Spruyt, MBChB, FRACP, FRAChPM; Lyle Galloway, MD CCFP; Michael F... more ... Robin Fainsinger, MD; Odette Spruyt, MBChB, FRACP, FRAChPM; Lyle Galloway, MD CCFP; Michael Fisch, MD MPH; Gina Kaye, MbChb MRCP(UK) MRNZCGP; John Hanson; Eduardo Bruera, MD; Donna Zhukovsky, MD FACP FAAHPM; Willem Landman, MBChB FAChPM ...

European Journal of Cancer, 2010

European Journal of Anaesthesiology, 2006

The purpose of this randomized, double-blind study was to compare 300 units of hyaluronidase per ... more The purpose of this randomized, double-blind study was to compare 300 units of hyaluronidase per one-half liter to 150 units per one-half liter in patients receiving brief infusions for subcutaneous hydration. Twenty-five evaluable patients were randomized to receive a local injection of 300 units of hyaluronidase or 150 units of hyaluronidase immediately before two 1-hr infusions of two-thirds dextrose 5% and one-third normal saline solution (500 cc volume). The following day a crossover took place, and patients received the alternate treatment before each of the two 1-hr infusions. The intensity and swelling as reported by the patient (visual analogue scale 0-100), and the intensity of edema and rash as assessed by the investigator (score 0-4) were not significantly different between groups. The patients' and investigators' final choice was also not significantly different. Patients could not distinguish between bolus and their previous experience with overnight clysis. Our results suggest that brief infusions are well tolerated for subcutaneous hydration of patients with advanced cancer. A concentration of 150 units of hyaluronidase per one-half liter is well tolerated in this population.

Cancer, 2007

BACKGROUND. The authors investigated how lymphopenia and low serum albumin levels correlate with ... more BACKGROUND. The authors investigated how lymphopenia and low serum albumin levels correlate with the prognosis of patients with carcinoma of unknown primary (CUP).

Breast Cancer Research and Treatment, 2010

We investigated the association between the risk of locoregional recurrence (LRR) and biological ... more We investigated the association between the risk of locoregional recurrence (LRR) and biological subtypes defined by hormonal receptors (HR) and HER-2 status in women with invasive breast cancer (BC). A total of 618 newly diagnosed BC patients were identified from a cancer registry within a single institution with standardized methods of tumor assessment for estrogen receptor (ER), progesterone receptor (PR), and HER-2. Patients were stratified based on surgical treatment, breast-conserving therapy (BCT) versus modified radical mastectomy (MRM), as well as biological subtypes: HR+/HER-2- (ER-positive or PR-positive, HER-2-negative), HR+/HER-2+ (ER-positive or PR-positive, HER-2-positive), HR-/HER-2+ (ER-negative and PR-negative, HER-2-positive) and TN (ER-negative, PR-negative and HER-2-negative). The association between clinicopathological factors, biological subtype and LRR was evaluated with univariate and multivariate Cox analysis. With a median follow-up of 4.8 years, the rate of LRR was 7.5%. On multivariate analysis, TN, tumor size ≥2 cm and lymph node (LN) positivity were associated with increased risk of LRR (P = 0.023, P = 0.048, and P = 0.0034, respectively). In BCT group, HR-/HER-2+ and LN positivity were associated with increased risk of LRR (HR 11.13; 95% CI 2.78-44.53; P = 0.0007 and HR 5.40; 95% CI 1.67-17.43; P = 0.0048, respectively). In MRM group, TN subtype and LN positivity were associated with increased risk of LRR (HR 4.72; 95% CI 1.53-14.52; P = 0.0069 and HR 3.23; 95% CI 1.44-7.29; P = 0.0047, respectively). Compared to HR+/HER-2-, HR-/HER-2+ treated by BCT and TN treated by MRM showed a significant decrease of 5-year LRR free survival (P = 0.0002 and P = 0.002, respectively). Tumor profiling using ER, PR, and HER-2 biomarkers is a promising tool to identify patients at high risk of LRR based on surgical treatment. Our findings suggest a different follow-up and locoregional treatment for patients with HR-/HER-2+ and TN subtypes.