Tumor Doubling Time

REFmENCES

Communicotimv fot thil IfJCIion will be publIIhsd ,. ",ac. and prioritle, permit. The commentl ,hould not nceed 350 worth in length, with tJ maximum of ~ re!etmee8; OM figure Of" ,able can be printed. E%C61JflonI mar 0CCfW ~ parlicuLJr circumlftJncBl. Contnbutlom mar include commen" an arlic1el publilhed in thilperiodlctJl, Of" they mar be repo'" 01 unique educaUonal character. SpBCl/ic permlaIon to publilh should be cited in tJ cooering letter Of" ~ III a postlcrip'.

Comparative Studiesof Selective Beta2 Adrenoceptor Agonist Aerosols To the Editor: With an increasing number of betaz adrenoceptor ago-

nists now available for the treatment of airway obstruction, comparative studies such as M. K. Tandon's are of interest

(Chut 1980; 77:429-31). However. there are several shortcomings which preclude the flndings in Dr. Tandon's group of 15 patients being necessarily relevant to others. Dr. Tandon gives no details of patient data such as initial pretreatment values for FEVl' pulse rate. electrocardiogram. presence of ventricular ectopic beats (VEB) or hypoxia. Furthermore. it was not stated whether patients were receiving corticosteroids or other potassium-depleting agents such as diuretics. Without such information it is not possible to decide whether these patients were more liIcely to develop VEBs than the majority of patients with airways obstruction. Measurements of FEY1 were taken only once 15 minutes after aerosol inhalation. Since muimal increases in FEV1 following inhalation of both salbutamol1 and fenoterol 2 aerosols occur after 30-60 minutes, bronchodilator efficacy in Dr. TandOD'S study was determined before the full response to each dose level had been achieved with either drug in which case it is d.ifBcu.lt to obtain meaningful comparisons. The "open" design of the trial also prejudices its findings. Before the release of fenoterol in Australia, saIbutamol was prescribed as the standard aerosol in most respiratory units. so it is presumed that most (if not all) patients would have been taking salbutamol as part of their regular bronchodilator therapy before the study. The consequent familiarity with salbutamol and unfamiliarity with fenoterol may have influenced the outcome. The results showed that at higher cumulative dose levels. fenoterol produced significantly faster heart rates than salbutamol, with a maximum mean difference of 11 beats per minute. Unfortunately. it was not stated at what stage (ie after how many inhalations) maximal bronchodilation was achieved so that determination of comparative therapeutic ratios is impossible. It is important that studies such as Dr. Tandon's are conducted, but their clinical iDterpretation will be facilitated by closer adherence to accepted methodology. including full details of patient characteristics will enable the reader to decide whether the findings are applicable only to the study group or whether they have wider implications. 1. Paul Seale. Ph.D., FRACP, Deparlment of Phtrrmocology, University of S"dney, Sydney, NSW, Australia

812 COMMUNICAnONS TO THE EDITOR

1 Zwi S, Kanarek DJ, McMurdo J. et aI. Clinical trial of salbutamol aerosol in chronic obstructive airways disease. Postgrad Moo J suppl 1971; 47:112-15 2 Heel RC. Brogden RN. Speight TM, et aI. Fenoterol: a review of its pharmacological properties and therapeutic efficacy in asthma. Drugs 1978; 15:3-32

To the Editor: In my original manuscript all these details of patient data were submitted, but I was asked to reduce the length of the paper before it could be published and hence one of the omissions was the table showing pre-treatment patient data on the two study days. Basal Cardiopulmonary Status Pa0 z (mm Hg)

Fenoterol 69.5 (65-73) FEV1 1.225 (0.75-2.l0) FVC 2.609 (1.54-3.90) Heart rate 79.16 (70-97) SystolicBP 1.22.4(96-150) Diastolic BP (74.0 (60-98)

Salbutamol 69.3 (65-73) 1.227 (0.76-2.20) 2.602 ( 1.62-3.90) 79.0 (70-97) 120.8 (96-146) 73.4 (60-100)

P NS NS NS NS NS NS

No patient with ventricular ectopic beats or hypoxia at rest was included in the study. There were four patients on longterm corticosteroid therapy. No patient was receiving treatment with diuretics. As the treatment with corticosteroids on the two study days was unchanged, any hypolcalemia resulting from treatment with corticosteroids should have affected reaction of both drugs on the cardiovascular system. I agree the maximal bronchodilator efficacy of both fenoterol and salbutamol occurs after 30-60 minutes. However, the important finding on this study was difference in the IacIc of cardio-selectivity of fenoterol as compared to saIbutamol when used in doses higher than normally recommended. Results of any "open" trial can be questioned. However, I do not believe that mere unfamiliarity with fenoterol would have influenced the unfavorable tachycardia and arrhythmias observed in such a large number of patients when given fenoteroL Following fenoterol, maximal bronchodilation had occurred in all patients after 7 puffs, whereas this occurred in all patients after 11 puffs of salbutamol With the exception of "open" design of trial, I believe I adhered to accepted methodology and I believe that the findings have wider implications and are not solely applicable to the study group . M. K. Tandon, M.D .• Senior Chut Specialist, &"tJfriation General HOS1Jitol, Hollywood, AumaUa

Tumor Doubling TIme To the Editor: In the section, Roentgenogram of the Month. in the July, 1980. issue of Cheal, Drs. Revathy Murthy and Robert F. Donohoe described a case of rapidly progressing diffuse pulmonary infiltration due to large cell carcinoma of the lung. They stated that "Tumor doubling time in lung neo-

CHEST. 79: 5. MAY, 1981

plasms depends somewhat on cell type, adenocarcinoma enlarging more rapidly than the epidermoid or small cell variety." To substantiate this, they referred to a report by Strauss.! Data reported by Strauss, myself,2 and others indicate that the doubling tinles of adenocarcinomas tend to be longer than those of other lung cancer-(ypes . Apparently, Murthy and Donohoe have interpreted this to mean that adenocarcinomas grow more rapidly. However, the longer the doubling tinle (the tinle it takes for a tumor to double its volume), the slower the growth rate .

WilliamWeiss,M.D. Professor of Medicine, Hahnemann MedicineCoUege, Philodelphla

1 Strauss MJ. The growth characteristics of lung cancer and its application to treatment design. Semin Oncology 1974; 1:167-74 2 Weiss W. Peripheral measurable bronchogenic carcinoma; growth rate and period of risk after therapy. Am Rev Resp Dis 1971; 103:198-208

To the Editor: We appreciate Dr. Weiss pointing out the error, which is really a typographical error that was not picked up when we read the galley proof. The mistake occurred when the editorial staff misconstrued what was written. The sentence should read "tumor doubling time in lung neoplasms depends somewhat on cell type, adenocarcinoma being much longer than that of epidermoid or small cell variety." We do want to point out at this time that doubling tinle at the best is a crude measurement of tumor growth and it does not give any indication of rates of proliferation of subpopulations of cells.! Doubling time may vary even within the same cell type and doubling time alone does not influence the progression of a radiographic picture. In the series reported by Dr. Chahinian, mean doubling time of epidermoid (95 days) was longer than that of adenocarcinoma (61 days), but this could be due to the disparity in the number of patients in each cell type groUp.2 As early as 1956, Collins,3 in describing the use of serial x-ray films in the measurement of doubling time, has pointed out that by the time x-ray diagnosis of a lesion is made, the majority of the doubling tinle in the life of the .tumor might have already occurred. Reoothy Murthy, M.D.

Medical Officer, Georgetown Medical Division, District of Columbia GeneralHospital, Washington, D.C.

Reprint requests: Dr. Murthy, D. C. General Hospital, Washington, D.C. 20003

1 Strauss M. Growth characteristics of lung Ca and its application to treatment design. Semin Oncology. 1974; 1:167-74 2 Chahinian P. Relationship between tumor doubling tinle and anatoclinical features in 50 measurable pulmonary cancers. Chest 1972; 61:340-45 3 Collins VP. Observations on growth rates of human tumors. Am J Boentgenol Had Ther ' Nucl Med 1956; 76:988-1000

CHEST, 79: 5, MAY, 1981

Postthoracotomy Suction To the Editor: Platitude or no, "history repeats itself." I note that Charles W. Van Way, III, (Chen 1980; 77:815-816), has rediscovered the Emerson high flow turbine apparatus. More surprising to me is the fact that thoracic surgeons continue to report "space problems" in the form of residual pneumothorax following open thoracotomy. Long ago, we demonstrated that the pressure range used by most surgeons was insuHicient.1 For over 20 years, I have used a minimum of minus 40 em of water suction routinely, following all thoracotomies, except total pneumonectomy. We always make sure to sever all adl1esions between lung and chest wall, mediastinum and diaphragm. Even in instances in which the lung does not expand fully, the mediastinum and diaphragm will shift to fl.ll the residual pleural space. No "tents," thoracoplasties, or other procedures are required to prevent "space problems." The strong suction holds the lung against the chest wall until a pleurodesis occurs. Even if air Ieakage persists along the tube tract, it will eventually seal after the tubes are withdrawn if pleurodesis is permitted to occur. High suction does not increase bleeding and does not "keep air leaks open" in our experience. Enerson and MeIntyre2 published an excellent study of chest suction devices and showed that the turbine type suction machine can maintain high flow with minimal effects on suction pressure. Many suction devices now on the market do not meet those requirements.

David V. Pecora, M.D., F.C.C.P. Chief, MedicalSen>ice, VA Medical and Regional Office Center, Wilmington, Delaware

1 Pecora DV. Early complications following resection for pulmonary tuberculosis. J Thorae Cardiovas Surg 1956; 32:216-25 2 Enerson DM, McIntyre J. A comparative study of the physiology and physics of pleural drainage systems. J Thorac Cardiovas Surg 1966; 52:40-46

To the Editor: I would like to thank Dr. Pecora for responding to my brief communication. His techniques of suction postthoracotomy are quite applicable to patients with pulmonary fibrosis or tuberculosis. I have found that 20 to 30 em of suction is adequate to produce expansion of the lung in most patients with normal lungs preoperatively, but the point is that one needs to use as much suction as needed. The suction system must have enough capacity to handle the air leak. In practice this means either the Emerson suction pump or the new vacuum regulator currently released by Ohio Medical Products. Either of these will accommodate peak flows 50 to 60 liters per minute. However, my letter was directed more at the problem of spontaneous pneumothorax. Unfortunately, it is quite standard practice to use the bubbler type regulator for this. As illustrated in my two patients, this can be worse than no suction at all. I believe that Dr. Pecora and I agree

COllUNICAnoNS TO THE EDITOR 813