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Case 1: 72-Year-Old Woman With Small Cell Lung Cancer

EP: 1 . Case 1: 72-Year-Old Woman With Small Cell Lung Cancer

Ep: 2 . case 1: extensive-stage small cell lung cancer background, ep: 3 . case 1: impower133 trial in small cell lung cancer, ep: 4 . case 1: caspian trial in extensive-stage small cell lung cancer, ep: 5 . case 1: biomarkers in small cell lung cancer, ep: 6 . case 1: small cell lung cancer in the era of immunotherapy.

EP: 7 . Case 2: 67-Year-Old Woman With EGFR+ Non–Small Cell Lung Cancer

Ep: 8 . case 2: biomarker testing for non–small cell lung cancer, ep: 9 . case 2: egfr-positive non–small cell lung cancer, ep: 10 . case 2: flaura study for egfr+ metastatic nsclc, ep: 11 . case 2: egfr+ nsclc combination therapies.

EP: 12 . Case 2: Treatment After Progression of EGFR+ NSCLC

EP: 13 . Case 3: 63-Year-Old Man With Unresectable Stage IIIA NSCLC

Ep: 14 . case 3: molecular testing in stage iii nsclc, ep: 15 . case 3: chemoradiation for stage iii nsclc, ep: 16 . case 3: pacific trial in unresectable stage iii nsclc, ep: 17 . case 3: standard of care in unresectable stage iii nsclc, ep: 18 . case 3: management of immune-related toxicities in stage iii nsclc.

Mark Socinski, MD: Thank you for joining us for this Targeted Oncology ™ Virtual Tumor Board ® focused on advanced lung cancer. In today’s presentations my colleagues and I will review three clinical cases. We will discuss an individualized approach to treatment for each patient, and we’ll review key clinical trial data that impact our decisions. I’m Dr. Mark Socinski from the AdventHealth cancer institute in Orlando, Florida. Today I’m joined by Dr Ed Kim, a medical oncologist from the Levine Cancer Institute in Charlotte, North Carolina; Dr Brendon Stiles, who is a thoracic surgeon from the Weill Cornell Medical Center in New York ; and Dr Tim Kruser, radiation oncologist from Northwestern Medicine Feinberg School of Medicine in Chicago. Thank you all for joining me today. We’re going to move to the first case, which is a case of small cell lung cancer. I’m going to ask Dr Kim to do the presentation.

Edward Kim, MD: Thanks, Mark. It’s my pleasure to walk us through the first case, which is small cell lung cancer. This is a case with a 72-year-old woman who presents with shortness of breath, a productive cough, chest pain, some fatigue, anorexia, a recent 18-pound weight loss, and a history of hypertension. She is a schoolteacher and has a 45-pack-a-year smoking history; she is currently a smoker. She is married, has 2 kids, and has a grandchild on the way. On physical exam she had some dullness to percussion with some decreased-breath sounds, and the chest x-ray shows a left hilar mass and a 5.4-cm left upper-lobe mass. CT scan reveals a hilar mass with a bilateral mediastinal extension. Negative for distant metastatic disease. PET scan shows activity in the left upper-lobe mass with supraclavicular nodal areas and liver lesions, and there are no metastases in the brain on MRI. The interventional radiographic test biopsy for liver reveals small cell, and her PS is 1. Right now we do have a patient who has extensive-stage small cell lung cancer. Unfortunately, it’s what we found. It’s very common to see this with liver metastases.

Transcript edited for clarity.

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Did you know that lung cancer is one of the most common cancers in the world? It affects both men and women and, apart from smoking, there can be other causes, such as: exposure to radon gas and carcinogenic substances or exposure to tobacco smoke. To talk about a clinical case of lung cancer we have designed this template full of illustrations of this organ. We have also added various images to help illustrate the information.

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• Volume 64, Issue 7
• A case of small cell lung cancer treated with chemoradiotherapy followed by photodynamic therapy
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• Department of Internal Medicine; College of Medicine, Chungnam National University Hospital and Cancer Research Institute, Jungku, Daejeon, South Korea
• Professor J O Kim, Department of Internal Medicine, Chungnam National University Hospital and Cancer Research Institute, 640 Daesadong, Jungku, Daejeon 301-721, South Korea; jokim{at}cnu.ac.kr

Here, we present the case of a 51-year-old man with limited-stage small cell lung cancer (LS-SCLC) who received concurrent chemoradiotherapy and photodynamic therapy (PDT). The patient was diagnosed as having LS-SCLC with an endobronchial mass in the left main bronchus. Following concurrent chemoradiotherapy, a mass remaining in the left lingular division was treated with PDT. Clinical and histological data indicate that the patient has remained in complete response for 2 years without further treatment. This patient represents a rare case of complete response in LS-SCLC treated with PDT.

https://doi.org/10.1136/thx.2008.112912

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Currently, patients with small cell lung cancer (SCLC) are treated with chemotherapy with or without thoracic radiotherapy. Radiation therapy is generally accepted as an essential component of limited-stage SCLC (LS-SCLC). However, the local failure rate after chemotherapy and radiotherapy remains high, ranging from 30% to 70%. 1 More effective means are needed to decrease the local recurrence rate.

Endobronchial photodynamic therapy (PDT) is used to treat patients who have central-type lung cancer, with the objective of palliation in advanced cases and curative intent in patients with early-stage disease. 2 3 Furukawa et al reported that PDT resulted in a complete response (CR) rate of 92.8% in patients with lesions of <1.0 cm; recurrences after a CR were seen in 9 of 77 lesions (11.7%) <1.0 cm. 4 When the extent of the tumour and the depth of the bronchogenic carcinoma have been evaluated, PDT can be an effective local treatment modality. 4

A few studies have described the treatment of SCLC using PDT. Moghissi et al 5 reported that 10 of 100 patients with advanced SCLC underwent PDT for palliation. Kato et al 6 and Okunaka et al 7 evaluated the effectiveness of PDT in the treatment of early-stage SCLC. However, none of these studies detailed a single case of SCLC treated with PDT.

Here, we present a case in which PDT was used with curative intent in a patient having endobronchial cancer, following standard treatment for SCLC and in addition to concurrent chemotherapy and radiotherapy.

CASE REPORT

A 51-year-old man presented to our clinic with a 6-month history of worsening dyspnoea on exertion. His symptoms included a nearly constant dry cough, diminished appetite without weight loss, and fatigue. He had previously been diagnosed as having diabetes mellitus with an uncontrolled glucose level and hypertension. The patient was a smoker with a ⩾40 pack-per-year history. The Eastern Cooperative Oncology Group performance status was grade 1.

The patient had undergone testing at an outside facility because of his symptoms; a plain chest x ray revealed opacity in the left lung field ( fig 1A ). As a result, the patient was diagnosed with pneumonia and treated with antibiotics. Despite antibiotic treatment, the resolution of pneumonic consolidation was delayed. Thus, the patient was referred to our hospital. Chest CT revealed an endobronchial protruding mass in the distal left main bronchus (LMB) with a near total collapse of the left lung and a small granuloma in the posterior segment of the right upper lobe ( fig 1B ). No evidence of mediastinal nodal disease or a metastatic focus was detected. Bronchoscopic examination showed functional vocal cords and a pedunculated mass in the LMB ( fig 1C ). Bronchoscopic washing and biopsies failed to demonstrate a specific cell type. A rigid bronchoscopic biopsy was performed, and the pathological examination confirmed the presence of small cell carcinoma based on immunostaining for CD56, synaptophysin, chromogranin and leucocyte common antigen (LCA) using the initial paraffin-embedded biopsy specimen. The results were consistent with SCLC. CT of the brain was normal. Therefore, the patient was diagnosed with LS-SCLC.

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Summary from the initial diagnostic investigation to last follow-up (A–C) Initial diagnostic investigation on June 2006. (D–F) Response evaluation after chemoradiotherapy in October 2006. (G and H) Positron emission tomography (PET)–CT without increased glucose uptake in October 2007. (I) There is no evidence of recurrence in December 2008.

Chemotherapy with cisplatin and irinotecan was initiated, but the chemotherapeutic regimen was changed to cisplatin and etoposide (EP) after one cycle due to grade 4 diarrhoea. Concurrent with the second and third cycles of EP, the total dose of thoracic radiation therapy was 45.6 Gy in 38 fractions (120 cGy per fraction). Treatment was given twice daily, at least 6 h apart, on weekdays. Thoracic radiation therapy was delivered with 6–10 MV photons using custom-made blocks. With re-expansion of the lung on plain chest x ray ( fig 1D ), the patient’s dyspnoea was found to be greatly improved. Post-treatment chest CT showed that the endobronchial protruding mass in the distal LMB was noticeably smaller, with a residual small soft tissue nodule in the left upper lobe ( fig 1E ). Bronchoscopy revealed a pedunculated mass in the orifice of the lingular division ( fig 1F ). To evaluate the size of the tumour and identify any unknown synchronous cancer, autofluorescence bronchoscopy was performed. We applied PDT to remove the remaining tumour completely, because high dose rate brachytherapy and stereotactic radiation techniques were not available in our hospital. The remaining tumour was treated with PDT after wire basket removal of the pedunculated mass via flexible bronchoscopy. A 2.5 mg/kg dose of haematoporphyrin derivate (Photogem, Moscow Institute of High Chemical Technologies, Russia) was administered intravenously 48 h before irradiation. Using a diode laser (wavelength = 630 nm; Biolitec, Jena, Germany), a light with a 3 cm cylindrical diffuser was introduced through the working channel of an autofluorescence fibreoptic bronchoscope. Illumination was carried out in the left second carina and orifice of the lingular division. The light dose was 100 J/cm. Bronchoscopy followed PDT for debridement and detection of PDT-related complications. No immediate complications occurred.

The complete disappearance of the tumour was confirmed pathologically by subsequent bronchoscopic biopsy and radiologically by chest CT after 4 weeks. No evidence of recurrence was observed from October 2006 to December 2008. One year after PDT, combined positron emission tomography (PET) and CT revealed no metabolic evidence of recurrence. Two years after PDT, chest CT and bronchoscopy demonstrated a complete response in this patient ( fig 1G,H ). The patient refused prophylactic cranial irradiation.

PDT as a local therapeutic modality often results in a CR of centrally located early-stage lung cancer. Kato et al 3 reported that PDT resulted in a CR in about 94% of patients with centrally located early lung cancer (squamous cell type) with a limited longitudinal extent (<1 cm). Moghissi et al 5 suggested that the benefits of PDT did not differ between patients with SCLC and non-small cell lung cancer (NSCLC); however, patients with SCLC may be deprived of PDT because SCLC grows rapidly and spreads to other organs earlier than NSCLC.

A combined modality consisting of thoracic radiotherapy and systemic chemotherapy is widely accepted as the standard treatment for LS-SCLC. For cases in which a tumour remains after standard treatment, clinicians should consider additional treatment modalities, including pneumonectomy, sleeve lobectomy or intraluminal brachytherapy. In this study, we had to consider the specific features of the tumour, which was located in the bronchial mucosa without invasion into the cartilaginous layer. Although the adverse effects of PDT include photosensitivity skin reaction (sunburn) in 5–28% of cases, respiratory complications in 0–18% and non-foetal haemoptysis in 0–7.8%, PDT is a safe method. 8

To reduce the local recurrence rate after PDT, both the extent and the depth of an endobronchial tumour must be known. Autofluorescence bronchoscopy and endobronchial ultrasonography (EBUS) may be useful as additional examination methods. 9 Miyazu et al 10 demonstrated that the depth of tumour invasion estimated by EBUS was accurate based on histological findings after surgical resection.

According to the guidelines released in 2003 concerning early-stage NSCLC, PDT should be considered as a treatment option in early superficial squamous cell carcinoma, especially for inoperable cases. 11 Regarding the extent and depth of an endobronchial lesion, PDT may be an effective treatment for superficial airway lesions ⩽1 cm in length, despite a diagnosis of SCLC. In this case, we applied PDT without confirming the depth of the lesion and without confirming that viable tumour remained after chemotherapy and radiotherapy, although radiological findings were highly suggestive of viable tumour. This case is the first report of the non-recurrence of SCLC.

This case suggests that PDT can be effectively used with curative intent.

• Brenner M ,
• Okunaka T ,
• Shimatani H ,
• Furukawa K ,
• Moghissi K ,
• Stringer M ,
• Miyazawa T ,
• Kurimoto N ,
• Mathur PN ,
• Sutedja T ,

Competing interests: None.

Patient consent: Obtained.

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A case of primary non-small cell lung cancer with synchronous small cell lung cancer

Department of Respiratory Disease, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241001, P.R. China

Synchronous multiple primary lung cancer is an uncommon and difficult to distinguish from metastatic disease. The present study reported an extremely rare case of a 66-year-old male with non-small lung cell cancer in the left lobe and synchronous small cell lung cancer in the right lobe. The diagnosis of multiple primary lung cancer not only depends on biopsy pathology, but also requires molecular biology results. This is of great significance for the management and prognosis of multiple primary lung cancer. The management of patients with non-small cell lung cancer-small cell lung cancer produces certain unique challenges, which may require individualized treatment modality that may not strictly comply with standard practices in the setting of a single tumor.

Introduction

Lung cancer is the most common cause of cancer-associated mortality worldwide ( 1 ). Multiple primary lung cancer (MPLC) is rare ( 2 ), ranging between 0.2 and 20% ( 3 ), which has ≥2 primary lung cancers with different pathological types ( 4 ). Two manifestations of MPLC exist: Metachronous or synchronous, and depending on which, their morphology and histology are similar ( 5 ). To distinguish MPLC from metastatic cancer in the lung or recurrence is difficult, however, it is of great significance for therapeutic management and prognosis. The diagnosis of MPLC not only depends on biopsy pathology, but also often requires molecular biology techniques, including DNA polity, gene mutations and microsatellite alteration ( 6 – 9 ). The present study reported a case of primary non-small cell lung cancer (NSCLC) in the left lobe and synchronous small cell lung cancer (SCLC) in the right lung lobe. The patient with synchronous MPLC tolerated two cycles of a chemotherapy regimen that consisted of etoposide (100 mg/m 2 of body-surface area) from one to three days and nedaplatin (75 mg/m 2 of body-surface area) on day one. The patient exhibited a favorable response, including loss of the dry cough and a reduction in the two lesions, observed by chest computed tomography (CT) during follow-up.

A 66-years-old male was referred to the Department of Respiratory Disease at Yijishan Hospital of Wannan Medical College (Wuhu, China) in April 2015 with a dry cough accompanied with blood in phlegm over the previous 1 month. The previous medical history of the patient was uneventful, with the exception of a 40 pack/year history of smoking. Physical examination revealed a rough respiratory murmur in each lung. Laboratory findings were within normal limits, with the exception of prostate special antigen (PSA) at 5.35 ng/ml. Chest CT images obtained in April 2015 revealed an irregular soft-tissue mass with a 9.6 cm maximum diameter, internal uniformity density in the middle-low right lobe close to pulmonary hilum, and a nodular high-density shadow with a 2.5 cm maximum diameter that was a lobulated lesion in the left upper lobe ( Fig. 1A and B ). The patient was positive for metastasis to the mediastinal lymph node. Fiber bronchoscopic biopsy was performed a few days later, which revealed squamous cell carcinoma in the left lobe and SCLC in the right lobe ( Fig. 2 ). Immunohistochemical staining of SCLC revealed a marked positivity for AE1/AE3, Syn, cluster of differentiation 56, thyroid transcription factor-1, p63 (few), Ki-67 (80%) and EMA. By contrast, the SCLC was negative for CgA(−), NapsinA and p40. The patient refused gene detection of squamous cell carcinoma in the left lobe due to expense. The patient tolerated two cycles of a chemotherapy regimen that consisted of etoposide (100 mg/m 2 of body-surface area) from 1–3 days and nedaplatin (75 mg/m 2 of body-surface area) on day 1. The patient exhibited a favorable response, including reduction in the dry cough, and reduction of the two lesions in the chest CT performed during follow-up ( Fig. 1C and D ). A limitation of the present case report is that only two cycles of etopiside combined with nedaplatin were administered in May and June 2015. The treatment with chemotherapy was interrupted due to the large expenditure.

Chest CT scans performed at different stages. (A and B) A chest CT scan performed in April 2015 showing a 96 mm tumor in the middle-low right lobe, and a 25 mm tumor in the left upper lobe, multiple mediastinal lymph nodes, mediastinal and lung windows. (C and D) A chest CT scan performed in June 2015 revealed a 28 mm tumor in the middle-low right lobe, and a patchy tumor of unknown size, multiple mediastinal lymph nodes, mediastinal and lung windows. CT, computed tomography.

Fiber bronchoscopy and biopsy pathology. (A) A new lesion was observed in the left upper lobe. (B) Hematoxylin and eosin staining revealed squamous cell carcinoma in the left lobe. (C) A new lesion was observed in the right middle lobe. (D) Hematoxylin and eosin staining revealed small cell cancer in the right lobe.

The present study reported an uncommon case of a 66-year-old male patient diagnosed with MPLC. Fiber bronchoscopy pathological biopsy revealed two completely different pathological types, which were squamous cell lung carcinoma in the left lobe and SCLC in the right lobe. The patient tolerated two cycles of a chemotherapy regimen that consisted of etoposide (100 mg/m 2 of body-surface area) from 1–3 days and nedaplatin (75 mg/m 2 of body-surface area) on day 1. The patient had a favorable response, including loss of the dry cough and reduction in the two lesions observed by chest CT during the follow-up.

To the best of our knowledge, MPLC is a special type of primary lung carcinoma occurring in one or both lung lobes, which may be ≥2 different pathological types ( 4 ). Two manifestations in MPLC exist: Metachronous or synchronous, and depending on which, their morphology and histology are similar ( 5 ). The mechanism of the MPLC remains to be fully understood, and only a few studies have addressed that it may be associated with field cancerization ( 10 , 11 ). Chang et al ( 12 ) reported the links between MPLC, and the epidermal growth factor receptor (EGFR) and p53 genes. Somatic alterations in EGFR were demonstrated, which can not only greatly improve the clonality assessment, but also affect the management of patients with MPLC. In addition, it is of significance to distinguish MPLC from metastatic carcinoma in the lung for the management and prognosis. The incidence of MPLC is attributed to the development of higher-resolution chest imaging techniques, positron emission computed tomography-CT, fiber bronchoscopy biopsy and percutaneous lung biopsy by CT fluoroscopy. The initial diagnostic criteria were established in 1975 by Martin and Melamed ( 4 ), and were updated by the American College of Chest Physicians (ACCP) ( 13 ). Different pathological categories is of great importance for the identification of MPLC ( 14 ). However, following the Martin-Melamed and ACCP criteria only distinguish certain MPLC types from metastases. Girard et al ( 7 ) confirmed that 3/7 patents with paired adenocarcinoma exhibited multiple primary lung tumors by means of EGFR/KRAS mutation testing. When it comes to similar pathological types, MPLC can be confirmed by means of DNA polity, gene mutations and microsatellite alteration ( 6 – 9 , 15 , 16 ). No standard guidelines exist for the management of MPLC. However, the current case demonstrated a few important principles. SCLC generally exhibits a higher growth fraction, a more rapid doubling time and earlier development of widespread metastases when compared with NSCLC ( 17 ). SCLC is highly sensitive to initial chemotherapy, particularly in the most common regimen (etoposide plus cisplatin), which can provide symptomatic improvement and prolonged survival ( 18 , 19 ). However, Veronesi et al ( 20 ) indicated that outcomes following surgery in patients with early SCLC were comparable to those in patients with NSCLC. The patient with an enlarged mediastinal lymph node exhibited squamous carcinoma combined with SCLC, therefore, that chemotherapy with etoposide and nedaplatin was performed. Therefore, if an MPLC patient is confirmed with synchronous SCLC and NSCLC, the appropriate chemotherapy regimen must be selected as quickly as possible.

In conclusion, the present study reported a case of MPLC with simultaneous SCLC and NSCLC. The management of patients with MPLC requires highly individualized treatment plans that are dissimilar to standard practices in the setting of a single tumor. Consideration must be given to the chemotherapy regimen that improve symptoms and prolongs survival.

Acknowledgements

The authors would like to thank Renguang Pei (Department of Interventional Therapy, Yijishan Hospital of Wannan Medical College, Wuhu, China) for providing assistance with writing and organization of this manuscript.

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