Lung cancer

Pulmonary Heteroplasia – additional opinion
Short Summary

66-year-old female was diagnosed, following persistent cough, with lung tumour with concomitant pulmonary nodules and a measurable enlargement of lymph nodes. FBS was positive for well differentiated neuroendocrine carcinoma and a needle biopsy revealed adenocarcinoma with associated neuroendocrine differentiation. Chemotherapy was initiated, and response evaluation following the fourth cycle showed either stability or an initiation of tumor response, but bone scintigraphy that was performed 6 months later revealed an area of increased uptake in the left hemithorax which could be suggestive of a secondary bone lesion. The expert agrees with the present therapeutic trial with Alimta, and in his opinion the tumor is non-operable.

Patient's Questions

1) Can you furnish an opinion on the treatment currently in progress?

2) What do you think of the possibility of a surgical operation for treating the neoplasia?

3) Can you explain what type of exam the Dotatoc-Pet is (Dr. S. report)?

Medical Background

Sex: F, Age: 66 years
Diagnosis: Pulmonary heteroplasia

On 5/2007, following persistent cough for some months, the patient was diagnosed having a non-operable tumor of her lung with satellite nodules. Two separate needle biopsies revealed a composed/non uniform histology, although both histologic samples were related to a neuroendocrine tumor:

a. well differentiated neuroendocrine carcinoma (typical carcinoid)
b. adenocarcinoma with associated neuroendocrine differentiation.

On 7/2007 chemotherapy (Cisplatin and Gemcitabine) was initiated.

On 9/2007 the first report about tumor markers revealed elevated levels:
ChromograninA (CgA) elevated to 380 and CEA elevated to 45. (It is unknown if these values were higher or lower than the pretreatment values which were not reported).

On 10/2007 a response evaluation following the fourth cycle of chemotherapy showed either stability (by CAT scan) or an initiation of tumor response (by PET scan). (The level of tumor markers was not reported at that time point).

On 11/2007 the treatment was switched to Tarceva for 1 month (the reasons for starting on Tarceva on that time and for stopping it just one month later were not reported).

On 12/2007 the level of CgA was found to have decreased to the normal level of 68 (!). (However, lacking the base line level of CgA [ previous to chemotherapy treatment] and the post chemotherapy level [previous to the treatment with Tarceva] it can't be determined whether this serological response represents a late response to the first 
administered chemotherapy, or a current response to the later administered Tarceva).

On 1/2008 a volumetric CAT scan demonstrated a moderate increase in size of a few satellite nodules at the edges of the main (and stable) nodular formation.

On 2/2008 following two months rest from treatment the value of CgA was still steady at the level of 58.

On 3/2008 a PET scan demonstrated persistence in the voluminous area of pathological accumulation of the radiopharmaceutical in the upper lobe of the right lung which appeared largely unchanged both in size and in the fixation gradient of the radiopharmaceutical, as compared to 10/2007. In addition there was complete normalization of the previously described fixation gradient of the radiopharmaceutical at the level of the II right and III left ribs.

On 4/2008 a whole body bone scintigraphy revealed a single area of increased uptake in the left hemithorax posterior arc of rib VII region which could be suggestive of a secondary bone lesion. (There is an intriguing discrepancy in the location of findings between the PET scan and the bone scintigraphy).

On 4/2008 the CgA value raised to 445 (!) representing a serological progression.

~~~~~


The most recent significant clinical information is as follows:
- on Nov 2007, admitted to DH to begin treatment with Tarceva 150 mg/day for 1 month;

- blood test on Dec 2007 for dosage of Chromogranin A = 68.0 (normal values 19.4 - 98.1);

- blood test on Jan 2008 for dosage of Somostatin = 20 (on empty stomach after 12 hours: < 26; 4 hours after meals </=80); NSE = 8.6 (less than 18.3); 5-OH- Urinary Indoleacetic acid = 9.6 (0.7 – 8.2).

- Total body multi-layer volumetric CAT scan -
o Cranial: normal.

o Chest: at the level of the upper lobe of right lung we have confirmation of the presence of a solid formation, unhomogeneous, containing some areas of aerial bronchogram. It is likely that this area is, in part, constituted by pathological tissue and, in part, by areas of atelectasic parenchyma. At the maximum extension point the lesion has a transverse diameter of 68 mm (previous 67 mm) and an anterior-posterior diameter of 100 mm (previous 97 mm) and is therefore stable. The central area appears more patchy. At the edges of the main nodular formation a few satellite nodules are observed, ranging from 11 mm to 21 mm in size (previous diameters 5 and 16 mm). These nodular formations therefore demonstrate a moderate increase in size. Small nodular irregularities, which could be of a fibrous nature, can be observed at the level of the left lung. No pleural effusion. Regular morphology of the cardiovascular structures of the mediastinum. The lymphadenopathy is insignificant at the mediastinic level with the exception of a lymph node of 10 mm at the carinal level.

o Abdomen-Pelvis: in the abdomen small cystic formation of the hepatic parenchyma are noted, but no secondary lesions. In the pelvis an increase was noted in the size of the uterus. The rest is normal.

As already reported in a previous PET exam, changes of osteoschlerotic type are confirmed at the second right and third left ribs, possibly repetitive in nature.

- blood test on Feb 2008 with Chromogranin A dosage 58.0 (19.4 - 98.1);

- PET of Mar 2008 - this test, compared with previous images performed in other locations, of which the most recent in October 2007, demonstrated a persistence in the voluminous area of pathological accumulation of the radiopharmaceutical in the upper lobe of the right lung, which appears largely unchanged in size and in the fixation gradient of the radiopharmaceutical. Slight hypercaptation of the radiotracer in an area of pleural thickening at the anterior arch of the IV left rib. Finally, complete normalization of the fixation gradient of the radiopharmaceutical is observed at the level of the II right and III left ribs.

- blood test on Apr 2008 with Chromogranin A dosage = 445 (19.4 - 98.1);

- CAT scan on April 2008 -
o Cranial: no significant elements

o Chest: at the level of the upper lobe of right lung we have confirmation of the presence of a solid formation, unhomogeneous, containing some areas of aerial bronchogram. It is likely that this area is, in part, constituted by pathological tissue and, in part, by areas of thickened-inflammatory parenchyma. At the maximum extension point the lesion has a transverse diameter of 70 mm previous 68 mm) and an anterior-posterior diameter of 12 mm (previous 10 mm) and is slightly larger. The central area appears less patchy. At the edges of the main nodular formation a few satellite nodules are observed, ranging from 11 mm to 34 mm in size (previous diameters 11 and 21 mm). These nodular formations therefore demonstrate a moderate increase in size. Small nodular irregularities, which could be of a fibrous nature, can be observed at the level of the left lung, stable. No pleural effusion. Regular morphology of the cardiovascular structures of the mediastinum. The lymphadenopathy is insignificant at the mediastinic level with the exception of a lymph node of 10 mm at the carinal level.

o Abdomen-Pelvis: in the abdomen small cystic formation in the hepatic parenchyma are noted, but no secondary lesions. In the pelvis an increase was noted in the size of the uterus. The rest is normal.

As already reported in a previous PET exam, changes of osteoschlerotic type are confirmed at the second right and third left ribs, possibly repetitive in nature.
 

Expert's Opinion

In response to your request I hereby offer my answers to the clarifications which were requested following the last second opinions of the two consultants.

A) Clarifications about the case history:

1. The treatment with Tarceva lasted not for one month, but for a period of approximately six months: from November 2007 until April 2008. Apparently it has been stopped in view of disease progression.

2. The patient is symptomatic as she has difficulty breathing (rarely in motion) and frequent cough. Her peripheral neuropathy, however, most probably represents persistent toxicity following her treatment with cisplatin.

3. Starting on May 2008 , the patient is under chemotherapy with ALIMTA. This is planed for 3-4 cycles. It is noted that treatment was preceded by 1 injection of Dobetin (7 days before starting Alimta) and 1 tablet of Folingrav (folic acid integrator), 270 mg per day for 7 days. I believe that Dobetin is going to be repeated following 9 weeks, and that 1 tablet of Folingrav is going to be taken daily until 3 weeks following the last dose of ALIMTA.

4. I have not been informed about actual levels of CEA and of CgA, measured at base line before the current treatment was initiated.

B) Questions and answers:

1. The treatment with Tarceva has been exhausted, as there is clear progression following 6 consecutive months of treatment.

2. Can you furnish an opinion on the treatment currently in progress?

I agree with the present therapeutic trial with ALIMTA (pemetrexed), hoping it will achieve at least a significant palliation.

3. What do you think of the possibility of a surgical operation for treating the neoplasia?

I agree with the stage of her disease as stated by Dr. S: T4N2-3M1.
There is no possibility of surgical treatment for a lung tumour at such an advanced stage.

4. Can you explain what type of exam the Dotatoc-Pet is (Dr. S. report)?

The Dotatoc-PET suggested by Dr. S. in his report consists with the Somatostatin receptor scintigraphy (SRS) which has been strongly recommended by me in May 2008. I agree with Dr. S. remark that the therapeutic efficacy of radioactive somatostatin analogues is limited in advanced tumours with diameters of +10cm even when these tumours present an adequate somatostatin receptor density.

Nevertheless, I still suggest that the patient undergoes what is considered a "classical" evaluation of neuroendocrine tumor of the lung by that Somatostatin receptor scintigraphy/ Dotatoc-Pet. This assessment of her tumor characteristics as well as an estimation of her chances to benefit from the consequent radionuclide treatment, should be conducted by a well experienced team.

I recommend that this evaluation be planned for the case that the current treatment has to be stopped, and be conducted before further a new line of chemotherapy is administered.

""