APOS Clinical E-Mail Update #16
16 March 2005

In this Update:

Is there any progress in chemotherapy for brain tumors?

Stupp R, Mason WP, van den Bent MJ.  Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma.  N Engl J Med 2005;352:987-996.


Rutkowski S, Bode U, Deinlein F et al.  Treatment of early childhood meulloblastoma by postoperative chemotherapy alone.  N Engl J Med 2005;352:978-986.


Hegi ME, Diserens AC, Gorlia T et al.  MGMT gene silencing and benefit from tomozolomide in glioblastoma.  N Engl J Med.  2005;352:997-1003.


DeAngelis LM.  Chemotherapy for brain tumors—a new beginning.  N Engl J Med

The New England Journal highlighted a series of advances in treatment of brain tumors.  These studies mark advances in chemotherapy treatment of adults with glioblastoma and show a benefit of chemotherapy for childhood medulloblastoma with less treatment-induced cognitive toxicity from radiotherapy to the young central nervous system.

Temozolomide given as adjuvant chemotherapy with radiotherapy after resection of glioblastoma prolonged life in a randomized study from 85 centers.  The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone in 573 patients.  Fortunately, temozolomide is fairly well tolerated with some nausea and myelotoxic effects.  Other than fatigue, the adverse effects are not psychiatric.

Certain patients, those patients with a methylated MGMT (O-methylguanine—DNA methyltransferase) promoter had more benefit from temozolomide.  Methylation compromises DNA repair by interfering with this DNA-repair gene.

Chemotherapy of early childhood medulloblastoma without radiation therapy holds promise, according to the report by Rutkowski et al.  The tumor was resected and then children received three cycles of cyclophosphamide, vincristine, methotrexate, carboplatin, and etoposide and intraventricular methotrexate.  Radiation of the central nervous system was avoided in two-thirds who did not have metastases in the nervous system.  The majority, 19 of 23 children, had asymptomatic leukoencephalopathy by magnetic resonance imaging, and their IQ scores were lower than a healthy comparison group, but not as low as patients who had received radiation as well in a previous trial.

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What happens to breast cancer survivors in the work place in Canada?

Maunsell E, Drolet M, Brisson J, Brisson C, Benoit M, Deschenes L.  Work situation after breast cancer: results from a population-based study.  J Natl Cancer Inst 2004;96:1813-22.


Schover LR.  Myth-busters: Telling the true story of breast cancer survivorship.  2004;96:1800-1801.

Middle-aged women treated for breast cancer in Quebec, Canada, have similar work situations to a control population sample who had never been diagnosed with cancer.  Three years after diagnosis, these 646 cancer survivors identified in the tumor registry and studied by telephone interviews, were slightly more (21% more) often unemployed than the 890 women in the comparison group.  For those who were still working, there was no change in working conditions.  The authors conclude that these results reflect women with newly diagnosed breast cancer who are working when diagnosed, who receive current multi-modal treatment, who have health care and insurance as part of a universal plan independent of employment status.  In general, the survivors themselves decided to stop working if they did stop.  They tended to attach less value to work after diagnosis.

Schover’s editorial juxtaposes the mythic stereotype of women devastated by breast cancer to the work from Quebec that showed more measured outcomes, including these results about employment.  The Quebec researchers have also shown that the rate of sexual dysfunction (50%) among women who have survived breast cancer is similar to that for matched postmenopausal women who have not had cancer.  Dissatisfaction with a spouse three months after the diagnosis of cancer correlated with break-up or divorce 8 years after diagnosis.  Quality of life did not significantly differ between women who had mastectomy or breast conservation.  Adjuvant chemotherapy causes the most physical and emotional morbidity.

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Do daughters resonate with the suffering of their mothers with breast cancer?

Cohen M, Pollack S.  Mothers with breast cancer and their adult daughters: the relationship between mothers’ reaction to breast cancer and their daughters’ emotional and neuroimmune status.  Psychosom Med 2005;67:64-71.

The distress of mothers with breast cancer and their adult daughters were highly related in a study of 80 mothers and their 80 daughters in Northern Israel.  Daughters’ distress also depended on the caregiving burden that the daughters’ perceived and how often they saw their mothers.

The distress of a mother with breast cancer affected daughters more than the stage of illness per se.  The degree of the mothers' psychological distress was related directly to the mothers' stage of cancer, and the daughters' distress was indirectly related to the mother's cancer stage.

The more distressed daughters had immune changes mediated by norepinephrine secretion like lower IL-2 induced NCA (natural cytotoxic activity) and decreased in vitro IL-2 and IL-12 secretion.  Cortisol mediated only IL-2 and daughters' distress.

The questionnaires included the symptoms checklist revised (SCL-90-R), a health status and health habits questionnaire constructed for the study, and four different scales, also composed for the study that measured frequency of meetings with mothers, degree of subjective caregiving burden, degree of disruption in daughters' lives, and activities for self-care.

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Can we still say that psychosocial intervention makes a difference for patients with Stage I or II melanoma?

Boesen EH, Frederiksen K, Thomsen BL, Dahlstrom K et al.  Psychoeducational intervention for patients with cutaneous malignant melanoma: a replication study.  J Clin Oncol 2005;23:1270-1277.

Melanoma is known for its variable course and its sensitivity to immunological treatments.  It is notable for its high rate of recurrence in the central nervous system.  Because of the anxiety-provoking risk for recurrence, NCCN recommends visits every 6 months for 2 years then annually for low-risk melanoma.  Surveillance is every 3-4 months for 2 years, then every 6 months 3 years for high-risk melanoma.

Psychosocial interventions have effectively reduced the distress related to the diagnosis.  Improvement has been associated with better immune parameters and in a landmark study with improved survival.  A six-week structured group intervention tailored to include health education, stress management, coping skills, and supportive group psychotherapy, as well as anti-anxiety and educational programs, was offered to patients with early stage melanoma.  They were taught simple relaxation exercises: progressive muscle relaxation, guided imagery or self-hypnosis, as well as problem solving and coping methods.  The interaction of the patients within the group provided a source of emotional support.1,2  The group that had the six- week treatment had a survival benefit at 5-6 years and documented differences in immune parameters but this effect weakened in the tenth year.3  Patients with moderate-to-high distress in a multi-disciplinary melanoma clinic were recently shown to benefit from a 4 session cognitive-behavioral intervention in a randomized controlled study compared to standard medical care.  The patients treated with the cognitive-behavioral intervention had less distress at 2 months.4

This randomized controlled study from Denmark, a replication of the Fawzy study, a comparison of six weekly sessions of two hours of psychoeducation (health education, enhancement of problem-solving skills, stress management, and psychological support) to a control found more active-behavioral and active-cognitive coping in the intervention group at six months.  The improvements, less fatigue, greater vigor, and lower mood disturbance, were only significant at 6 months but not 12.  The authors call attention to the temporary nature of the effect and emphasize that patients distressed at the time of treatment may have greater benefit from the intervention.  Believing that one can cope predicts better coping.  One role of psychoeducation is to strengthen that belief.

1.  Fawzy FI, Cousins N, Fawzy N, et al.  A structured psychiatric intervention for cancer patients:  1. Changes over time in methods of coping and affective disturbance.  Arch Gen Psychiatry 1990;47:720-725.

2. Fawzy FI, Kemeny ME, Fawzy N, et al.  A structured psychiatric intervention for cancer patients:  2. Changes over time in immunological measures.  Arch Gen Psychiatry 1990;47:729-735.

3. Fawzy FI, Canada AL, Fawzy NW.  Effects of a brief, structured psychiatric intervention on survival and recurrence at 10-year follow-up.  Arch Gen Psychiatry.  2003;60:100-103.

4. Trask PC, Paterson AG, Griffith KA, Riba MB, Schwartz JL.  Cognitive-behavioral intervention for distress in patients with melanoma.  Cancer 2005; 98:854-864.

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Would you rather have watchful waiting or active surveillance for prostate cancer?

Parker C.  Watchful waiting, temporarily deferred therapy, or active surveillance?  J Clin Oncol 2005;23:1322-1336.

It turns out to be psychologically important how patients interpret the words "watchful waiting" as they apply to management of low-grade prostate cancer.

Parker wrote a letter to the editor of J Clinical Oncology suggesting the term active surveillance in response to the article by Carter et al.1 on temporarily deferred therapy of prostate cancer.  Parker argues that this method of active surveillance could be termed radical treatment based on biochemical or histological evidence of disease progression during close monitoring.  This method would give curative treatment to the minority of patients who need it.  In his view "active" surveillance "requires a clear definition of the indications for radical treatment (usually based on PSA doubling time and the results of repeated biopsies)."

1.Carter CA, Donahue T, Sun L, et al: Temporarily deferred therapy (watchful waiting) for men younger than 70 years and with low-risk localized prostate cancer in the prostate-specific antigen era.  J Clin Oncol 2003;21:4001-4008.

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How can we use our trained intuition and correct for predictable bias?

Redelmeier DA.  The cognitive psychology of missed diagnoses.  Ann Intern Med 2005;142:115-120.

The topic of the best seller Blink by Malcolm Caldwell is the nature of instantaneous unconscious trained reasoning.  Redelmeier adds to clinical medical training by highlighting the nature of rapid clinical judgments and the ways that rapid reasoning might fail.  Thankfully, he also offers methodical corrective measures for each type of error.  Physicians may make a judgment based on their most recent past cases instead of the base rate of the syndrome.  Redelmeier says, "If you hear hoof beats, think about horses not zebras."  The anchoring heuristic is defined as the tendency for the clinician to rely on the first impression.  This tendency is balanced by careful reconsideration of new data.  Framing effects, the tendency to be swayed by subtle wording, can be minimized if a case is reviewed from different perspectives.  Sometimes physicians show undue deference to authority or technology; both must be put in perspective later when a little distance and perspective is available.  Premature closure is the tendency to espouse narrow-minded belief in a single idea .Redelmeier suggests that the defense for this error is careful consideration of the diagnosis that you would not want to miss.

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How do we measure the impact of distress in cancer patients?

Akizuki N, Yamawaki S, Akechi T, Nakano T, Uchitomi Y.  Development of an impact thermometer for use in combination with the distress thermometer as a brief screening tool for adjustment disorders and/or major depression in cancer patients.  J Pain Symptom Manage 2005;29:91-99.

Akizuki and his colleagues have added to the subtlety of the distress thermometer by adding an impact thermometer in order to improve specificity without sacrificing brevity and good sensitivity.  The Impact Thermometer is a one-item questionnaire with an 11-point Likert scale that has the same thermometer-like format at the Distress thermometer.  The scores from 0 to 10 indicate the impact of distress on daily life activity.  The authors used the Impact Thermometer to distinguish adjustment disorders from major depression.  Impact indicates impairment of social functioning as an essential feature of the formal psychiatric diagnosis.  The researchers presented both thermometers on a single sheet of paper.  In a group of 295 cancer patients, these thermometers, the Hospital Anxiety and Depression Scale, and formal diagnosis by psychiatrists showed a sensitivity and specificity of 0.82 and 0.82 for adjustment disorder and major depression if 3/4 on the Distress thermometer and 2/3 on the Impact thermometer were used as cut-off scores.  The authors found that this double thermometer was brief and effective for routine screening and comparable to the Hospital Anxiety and Depression Scale.

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Donna B. Greenberg, MD, Associate Professor of Psychiatry at Harvard Medical School and Psychiatric Consultant in the Massachusetts General Hospital Cancer Center, Dana Farber Partners Cancer Care