La Vecchia, C.

Levi, F.

Lucchini, F.

Negri, E.

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Annals of Oncology 10: 1529-1532. 1999.Letters to the editorRadiation pneumonitis after local-regional radiotherapy followingautologous stem-cell transplantfor high-risk breast cancerWe have read the article by Moore et al. [1] regarding thetoxicity and outcome of high-dose chemotherapy with stem-cell support followed by local and regional radiotherapy in acohort of 103 patients with high-risk breast cancer. Radiationtherapy to the breast (or chest wall) plus regional lymph nodeareas is aimed at decreasing the unacceptably high rate ofloco-regional relapses (33% in Peter's report [2]) seen inpatients with metastasis to > 10 axillary lymph nodes aftersurgery plus high-dose chemotherapy. Indeed, it significantlydecreases the rate of loco-regional relapses in this patientpopulation, as shown by Moore et al. [1]. However this isachieved at the cost of substantial toxicity for some patients.We have recently analyzed the toxicities of local-regionalradiotherapy following high dose chemotherapy with carbo-platin, tiothepa and cyclophosphamide [3] with autologousstem-cell transplant in a cohort of 31 patients with high-riskbreast cancer (>10 axillary nodes: 7 patients; 4-9 nodes: 7patients or stage III: 17 patients). All patients received thescheduled dose of radiation (electron beam: 5500 cGy to thebreast or chest wall, and 4500 cGy to the axillary, supra-clavicular and internal mammary lymph node areas) relativelyearly after transplant (median time from stem-cell infusion toinitiation of radiotherapy: 49 days, range 19-84 days; medianduration of radiotherapy: 43 days, range 36-54 days), and onlyfive patients (16%) required temporary discontinuation ofradiation for one to two weeks following mild fever of unknownorigin (3 patients) and acute pneumonitis (2 patients). Radiationpneumonitis was a frequent toxicity in this series. Ten patients(32%) had acute pneumonitis. Dry cough and fever were thepresenting symptoms. Most patients underwent an unsuccess-ful work-up for infectious pneumonia often including admis-sion. The symptoms subsided with corticosteroid therapy.We feel it should be emphasized that radiation pneumoniais a frequent cause of fever in patients with high-risk breastcancer undergoing local-regional radiation therapy after high-dose chemotherapy with stem-cell support.J. L. Marti, A. Tres, CVelilla, P. Lopez, M. D. Garcia,D. Isla & J. I. MayordomoDivision of Medical Oncology, University Hospital,Zaragoza, SpainReferences1. Moore HCF, Mick R, Solin LJ et al. Autologous stem-cell trans-plant after conventional dose adjuvant chemotherapy for high-riskbreast cancer: Impact on the delivery of local-regional radiationtherapy. Ann Oncol 1999; 10: 929-36.2. Peters WP, Ross M. Wredenburgh JJ et al. High-dose chemo-therapy and autologous bone marrow support as consolidationafter standard-dose adjuvant therapy for high-risk primary breastcancer. J Clin Oncol 1993; 11. 1132-43.3. Antman K, Ayash L, Elias A et al. A phase II study of high-dosecyclophosphamide, thiotepa, and carboplatin with autologous mar-row support in women with measurable advanced breast cancerresponding to standard-dose therapy. J Clin Oncol 1992; 10:102.Urinary bladder cancer death ratesin EuropeSeveral risk factors have been associated with bladder cancerrisk, including cigarette smoking, occupational exposure toaromatic amines and other chemicals, bladder infections, se-lected aspects of diet, and the use of some drugs such asphenacetine-containing analgesics, chlornaphazine and cyclo-phosphamide [1]. In the US [2], Britain [3] and Italy [4] 50°/<r-70% of bladder cancers in men, and 20%-35% in women wereattributable to cigarette smoking, and 5%-10% to occupa-tional exposures. Changes in exposure to these two major riskfactors, therefore, may largely explain trends registered inmortality from the disease, mostly for males.In 1990-1994, most of the age-adjusted (world standardpopulation) mortality rates for men in Europe ranged between5 and 8 per 100,000. Only Denmark (8.9), Spain and Italy (8.6),and Hungary (8.1) had rates over 8/100,000. Sweden and otherNordic countries had low rates. Rates for women were between1 and 3/100,000 in most European countries [5, 6]. An age-period and cohort model showed that in most western Europemortality increased up to the generations born around 1920 to1940, and declined thereafter [7]. In the United States, thedeclines had started earlier, and bladder cancer mortality hasbeen declining in white and black populations of both sexessince the late 1970s [8].Figure 1 gives trends in age-standardized (world standard)all age and truncated 35-64 years bladder cancer mortalityfrom 1955 to 1994 in the European Union, derived from theWorld Health Organisation database [9, 10]. Overall age-standardized rates in males increased from 4.5/100,000 ininx.4--c -a- Tg B- B—E1970 1975 '9E0 1955C A L E N O A R Y E A R S2C30f t U U S , i l l o g nfemes, ss-nFigure I. Trends in age-standardized (per 100.000. world standard)mortality rates from bladder cancer in the 15 countries of the EuropeanUnion, 1955-1996.1530ooooo1970 1975 1990 1985C A L E N D A R Y E A R SI 1 1 I S , o i l O J I S F I I U E S . i l l o g na B oF [ « U [ S . ) 5 - 6 <0 0 0Figure 2 Trends in age-standardized (per 100,000, world standard)mortality rates from bladder cancer in six eastern European countries,1955-19961955-1959 to 7.4 in 1985-1989, and levelled off thereafter to6.4/100,000 in 1995-1996. Truncated rates were 5.4/100,000males in 1955-1959, peaked at 6.5 in 1980-1984, and declinedto 4.6/100,000 males in 1995-1996. For females, overall ratesincreased from 1.4/100,000 in 1955-1959 to 1.6 in 1985-1989,and remained approximately stable thereafter. Truncated ratesin females remained around 1.4/100,000 between 1955 and 1980,and declined thereafter to reach 1.1/100,000 in 1995-1996.Corresponding values for six eastern European countriesproviding data (Bulgaria, Hungary, Poland, Romania, CzechRepublic, Slovakia, i.e., former Czechoslovakia) are given inFigure 2. Overall bladder cancer rates for males in easternEuropean countries rose from 4.9 in 1955-1959 to 7.1/100,000 in1995-1996. Truncated rates declined from 6.5/100,000 in 1955-1959 to 5.2/100,000 in 1970-1974, but steadily increased there-after to reach 7.5/100,000 in 1995-1996. In females, overall ratesslightly increased from the early 1970s (1.0/100,000) to reach 1.3/100,000 in the mid-1990s. Truncated rates, after a declinebetween the mid 1950s (1.6/100,000 females) and the early 1970s(1.0/100,000), remained around 1.2/100,000 until the mid 1990s.The present figures indicate that bladder cancer mortalityhas started to decline for males in the European Union aboutten years later than in the United States. In Eastern Europe, incontrast, bladder cancer mortality is still appreciably upwardsin males, is now higher than in the European Union, and hasstarted to rise in females, too. This indicates that there weresubstantial delays in controlling major risk factors for bladdercancer in these countries, mainly tobacco and occupationalexposure to carcinogens [9. 10].AcknowledgementsThis study was supported by the Swiss League against Cancer(KFS 497-9-1997) and the Italian Association for CancerResearch.C. LaVecchia,1'2 F. Lucchini,3 E. Negri1 & F. Levi3'4xIstiluto di Ricerche Farmacologiche 'Mario Negri'; 2Isti-tuto di Statistica Medica e Biometria, Universita degliStudi di Milano, Milano, Italy; 3Regislre Vaudois desTumeurs and Unite d'epidemiologie du cancer, Institutuniversitaire de medecine sociale el preventive, CentreHospitalier Universitaire Vaudois, Falaises 1, 1011 Lau-sanne, Switzerland; 4Authorfor correspondenceReferences1 La Vecchia C, Airoldi L. Human bladder cancer: Epidemiolog-ical, pathological and mechanistic aspects. In Draper CC. DybingE, Rice JM, Wilboum JD (eds)' Species Differences in Thyroid,Kidney and Urinary Bladder Carcinogenesis. IARC ScientificPublication No. 147. Lyon: International Agency for Research onCancer 1999; 139-57.2. Hartge P, Silverman D, Hoover R et al. Changing cigarette habitsand bladder cancer risk: A case-control study. J Natl Cancer Inst1987; 78: 1119-253. Moolgavkar SH, Stevens RG Smoking and cancer of bladder andpancreas: Risks and temporal trends. J Natl Cancer Inst 1981; 67:15-23.4. D'Avanzo B, La Vecchia C, Negri E et al. Attributable risks forbladder cancer in northern Italy. Ann Epidemiol 1995; 5: 427-31.5. Levi F. Lucchini F, Boyle P et al. Cancer incidence and mortalityin Europe, 1988-1992. J Epidemiol Biostat 1998; 3: 295-373.6. Levi F, Lucchini F, Negri E, LaVecchia C. Worldwide patterns ofcancer mortality, 1990-1994. Eur J Cancer Prev 1999; 8: 381-400.7 LaVecchia C. Negri E, Levi F et al. Cancer mortality in Europe'Effects of age, cohort of birth and period of death. Eur J Cancer1998; 34: 118-41.8 Anonymous. Stat Bite. US urinary bladder cancer death rates.J Natl Cancer Inst 1999; 91: 1362.9. Levi F, Lucchini F, Negri E et al. Cancer mortality in Europe,1990-1994, and an overview of trends from 1955-1994. Eur JCancer 1999; 35: 1477-516.10. Levi F, Lucchini F, La Vecchia C, Negri E. Trends in mortalityfrom cancer in the European Union, 1955-1994. Lancet 1999;354: 742-3.Elevation of urinary porphyrin levelsfollowing gemcitabine administrationA 67-year-old man with a diagnosis of porphyria cutanea tarda(PCT) and HCV-positive well compensated (Child-Pugh A)liver cirrhosis came to our institution because of ultrasono-graphic evidence of a 4 cm liver lesion, discovered during aroutine examination. Cytologic examination of a fine-needlebiopsy (FNAB) of this lesion was suggestive of adenocarcino-ma. A laparotomy showed diffuse abdominal adenomegalies.Histologic examination of an intraoperatory liver mass biopsyand a resected retroperitoneal lymph node showed the presenceof a metastatic cholangiocarcinoma. After an uneventful post-operative recovery, the patient agreed to participate in aninvestigational protocol with gemcitabine that was adminis-tered at the dosage of 1.000 mg/m2 on days 1, 8 and 15,repeated every 28 days. Twenty-four to seventy-two hours aftereach administration, the patient noticed dark urine. Urineexamination was negative for the presence of blood or biliarypigments. Before the second chemotherapy cycle, the assay fortotal urinary1 porphyrins was within normal values (78 ug/1.normal range 50-200 ug/1). A new assay performed on urinecollected 48 hours after the first administration of the second

Urinary bladder cancer death rates in Europe

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