Running Title: Ching,S.M. etc. Delay in diagnosis of lung cancer:A case report and review of literature.

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Ching, S.M.1 (MD, MMed Fammed), Chia, Y.C.2 (MBBS, FRCP), Cheong,A.T.3 (MBBS, MMed Fammed)

1Department of Family Medicine, Faculty of Medicine andHealth Sciences, 43400 UPM Serdang, Selangor D.E., Malaysia

siewmooi@medic.upm.edu.my

2Department of Primary Care Medicine, Faculty of Medicine,University of Malaya, 50603 Kuala Lumpur, Malaysia,

Affiliation: Curtin Health Innovation Research Institute,Faculty of Health Sciences, University of Curtin,

Australia

Corresponding Author:Name: Ching Siew MooiAddress: Department of Family MedicineUniversiti Putra Malaysia 43400 Serdang, Selangor Malaysia Email@address:siewmooi@medic.upm.edu.my,chingsmlcl2004@yahoo.com

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ABSTRACT

Keywords: Adenocarcinoma, Lung cancer, female patient, delaydiagnosis, non-smoker

This case report highlights the delay in diagnosis of adenoma carcinoma of lung in a female patient who has never smoked. It took three months to reach the diagnosis of stage IV lung carcinoma despite the presence of symptoms and an abnormal chest X-ray finding from the beginning. The clinical characteristics and predictors of missed opportunities for early diagnosis of lung cancer are discussed. In this case, patient and doctor factors contributed to the delayin diagnosis.Thus, Early suspicions of lung cancer in a woman presenting withrespiratory symptoms despite being a non-smoker is important inprimary care setting.(100 words)

Keywords: Adenocarcinoma, Lung cancer, female patient, delaydiagnosis, non-smoker

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INTRODUCTIONCarcinoma of the lung is the second commonest cancer among men and the sixth most common cancer among women in Peninsular Malaysia (Ministry of Health, 2008). The male to female ratio is approximately 3:1 (Ministry of Health, 2008). Hence, lung cancer is considered a disease of men and more common among smokers. Being female and non-smoker, this particular group of patients, is particularly vulnerable to a delay in presentation and diagnosis of lung cancer, a result of low suspicions by the attending physicians. Lung cancer is notoriously known to present in advanced stages bythe time it is diagnosed and this unfortunately means a poorprognosis (Michael D Peake, 2008). Only approximately 50% ofpatients survive for less than six months from the time ofdiagnosis and only one quarter are still alive one year after thediagnosis (Michael D Peake, 2008). The following case studyprovides an example that a greater sense of awareness is neededby physician when approaching a female, non-smoker patient butwith suspicious symptoms for lung cancer.

CASE STUDYA 64-year-old para 4, postmenopausal housewife with

underlying hypertension on diet control complaining of cough, shortness of breath, haemoptysis and occasional chest pain for the past 10 weeks. Otherwise, she was active in terms of the activity of daily living. She went for an x-ray in the general practitioner clinic and treated as for community-acquired pneumonia. She was reassured no need to be worried as a course ofantibiotic would be prescribed for her condition. She was neithergiven a follow up or referral letter. Her symptoms were not improve two week following the antibiotic, thus the family members were quite concerned about her unresolved symptom and decided to come to see the author for a second opinion instead ofgoing back to the previous doctor.

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She was not a primary or secondary smoker, denied fevers, night sweat, chronic cough, dark urine or leg swelling and did not have any other known risk factors for developing lung cancer.There was no family history of malignancy as well.

On examination, she appeared thin but no jaundice. Dilated vein noted on the anterior chest wall and fingers clubbing were present. However, there was no cervical lymphadenopathy noted. Her respiratory rate was 18 breaths per minute, blood pressure of 156/ 80 mmHg, pulse rate of 80 beat perminute with a BMI of 20.1 kg/m2.

The chest expansion and air entry were reduced together with stony dullness noted on right lower lung. There was no crepitations or rhonchi heard. On top of that, there was a palpable liver, firm in texture and measured about 2cm below the right costal margin. Breast and spine examination were normal.

InvestigationsFull blood count RESULT REFERENCE RANGE

Hb 11.8 ↓ (12.0-15.0 )g/LWBC 4.1 (4-10) X109/LPlatelet 336 (150-400) X109/LESR 34 mm/hr

Tuberculosis workout RESULT REFERENCE RANGESputum Culture andsensitivity

Normal upperrespiratorytract flora

Sputum Acid Fast Bacilli x3

negative

Mantoux test No induration (<10 mm)

Her chest X-ray done in the clinic showed an ill-defined opacityand consolidation at the right middle lobe with an ill-definedmass obscuring right heart border. There was large right pleuraleffusion with an elevated right horizontal fissure seen (Figure1).

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Figure 1: Chest radiography of the patient

Computed tomography (CT) scans and bronchoscopic guided biopsy ofthe chest were done 2 weeks later. There was an irregularheterogeneously enhancing mass with necrotic component at theright lungs lower lobe medial segment, measuring 4.5 x 4.3x 7cm.It showed a metastatic nodular lesion in the apical segment ofthe right lung lower lobe. Left lung was clear and right hilarlymph node was enlarged by 2.1cm. Right pleural effusion was apresent and two hypodense lesion noted in the liver as well(Figure 2).

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Figure 2: Chest CT scan of the patient after given chemotherapy

Histopathology examination revealed there was moderatelydifferentiated adenocarcinoma (stage 4 1b) of the lung. Thestatus on the eGFR mutation status was not done.

Despite being treated with biologic agents (Gefitinib), thepatient developed brain metastasis, her condition deterioratedand she succumbed to the disease 18 months after diagnosis.

DISCUSSIONDelay in diagnosis of cancer is associated with substantial disability(Phillips RL Jr, Bartholomew LA, & Dovey SM et al, 2004) and malpractice claims(Singh H, Sethi S, & Raber M et al, 2007). Delayed diagnosis is also one of the modifiable factors that contribute to poor prognosis in lung cancer. This could be a quite common scenario in the primary care setting as Malaysia neither have any established cancer control program, nor any policy for early detection of any cancer. Furthermore, the primary care doctors are often very busy and could easily miss the early signs and symptoms of lung cancer especially if the

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suspicion is not kept at the back of the mind. Basically, delays could be due to three factors. Firstly, the delay could be due topatient factors whereby the patient delays their decision in consulting a doctor when their symptoms first presents. Then they may have poor adherence to the advice or appointment; or they may ask for a second opinion from different health care centres which subsequently can contribute to late diagnosis (Corner J, Hopkinson J, & Roffe L, 2006). Secondly, physician factors such as misinterpreting symptoms and treating it as some other disease which share similar presentations causes a delay inreferral. Thirdly, “system” factors where a long waiting period for appointments, imaging or diagnostic tests (Devbhandari MP, Bittar MN, & Quennell P et al, 2007) often cause further delay. Besides all the above factors, there is more delay for treatment to be initiated upon diagnosis by the specialist. In other words,it may take around 3 to 7 months from the first symptom presentedby the patients to starting treatment (Eija-Riitta Salomaa, Susanna Sällinen, Heikki Hiekkanen, & Kari Liippo, 2005). However, according to a study the duration of delay in diagnosinglung cancer could be shortened to 19 days if the predictors of missed opportunities for early diagnosis of lung cancer can be recognised (Hardeep Singh et al., 2010). The predictors of missed opportunities in making early diagnosis identified from this study are: recurrent bronchitis (odds ratio [OR], 3.31; 95%CI, 1.20 to 9.10), failure in following up an abnormal chest X-ray (OR, 2.07; 95% CI, 1.04 to 4.13) and completion of rst fineedle biopsy (OR, 3.02; 95% CI, 1.76 to 5.18). For the clinicalfeatures, haemoptysis is one of the cardinal and pertinent features of lung cancer (Hamilton W, Peters TJ, Round A, & Sharp D, 2005).

In this case; there was some delay before the patient visited thedoctor as she was not able to interpret her symptoms as beingserious. Even though it may be quite challenging for the doctorwho first saw her to reach the correct diagnosis, as herpresenting symptoms could suggest pneumonia or pulmonarytuberculosis which is relatively more prevalent in Asiancountries including Malaysia. Furthermore, it is common for

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patients with lung cancer to present initially with chestinfection – reference Hardeep et al).

However, by right; the patient should be given a safety nettingthat she needed to come back if the condition not improved orscheduled for a follow-up by the initial attending doctor. Testfor sputum acid-fast bacilli (AFB) should be performed in view ofthe high prevalence of pulmonary tuberculosis in the localsetting. In case, if the sputum AFB is normal in the presence ofan abnormal chest X-ray finding, the patient should be referredto hospital for an early CT scan appointment or to be seen earlyby the chest physician for further evaluation.

CONCLUSION

In conclusion, a higher index of suspicion of lung cancer is needed in symptomatic non smoker, female patients. The clinical features may mimic other lung conditions, thus close follow-up for response of patient to treatment is of utmost importance and if there is no response then referral is warranted.

References

Corner J, Hopkinson J, Roffe L: Experience of health changes and reasons for delay in seeking care: A UK study of the months priorto the diagnosis of lung cancer. . Soc Sci Med 62:1381-1391, 2006.

Devbhandari MP, Bittar MN, Quennell P et al: Are we achieving thecurrent waiting time targets in lung cancer treatment? Result of a prospectivestudy from a large United Kingdom teaching hospital.J Thorac Oncol 2:590-592, 2007.Eija-Riitta Salomaa, Susanna Sällinen, Heikki Hiekkanen, et al.: Delays in the Diagnosis and Treatment of Lung Cancer. . CHEST 128:2282-2288, 2005.

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Hamilton W, Peters TJ, Round A, et al.: What are the clinical features of lung cancer before the diagnosis is made? A population based case-control study. Thorax 60:1059-1065, 2005.

Hardeep Singh, Kamal Hirani, Himabindu Kadiyala, et al.: Shortening the diagnostic and treatment delay times might be possible with if the general practitioner can have a higher suspicion of this disease, especially among those ex-smoker and nonsmokers. JOURNAL OF CLINICAL ONCOLOGY 28:3307-3315, 2010.

Michael D Peake: Lung cancer and its management. Medicine 36:162-167, 2008.

Ministry of Health. (2008). The Third Report of the National Cancer Registry, Malaysia. . Retrieved Accessed at 16 December 2012 from http://www.radiologymalaysia.org/Archive/NCR/NCR2003-2005Bk.pdf.

Phillips RL Jr, Bartholomew LA, Dovey SM et al: Learning from malpractice claims about negligent, adverse events in primary care in the United States. Qual Saf Health Care 13:121-126, 2004.

Singh H, Sethi S, Raber M et al: Errors in cancer diagnosis: Current understanding and future directions. J Clin Oncol 25:5009-5018, 2007.

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