Pulmonary heteroplasia_3
Short Summary

66-year-old female was diagnosed, following persistent cough, with non-operable tumor of her lung with satellite nodules, and chemotherapy was initiated (first Cisplatin and Gemcitabine, and then switched to Tarceva). Response evaluation following the fourth cycle of chemotherapy 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.

 

Patient's Questions
1)            How would you assess the progression of the disease?

 
2)            What is the prognosis?

 
3)            Do you suggest any possible diagnostic measures to complement those conducted so far?

 
4)            Any other treatments to use?
Medical Background

Patient's History
Sex: F, Age: 66 years
DiagnosisPulmonary 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 à
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 2008à, 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 à
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

 
A) Notes on the presented data:
A1) The last evaluation of the patient's disease following chemotherapy with Alimta is based on the CT dated 7.2008. It shows a disease arrest status, based on the lack of change in the overall dimensions of the main tumor lesion. However, a meticulous interpretation of that CT pictures in comparison to those from 4.2008 shows an increase of thick components and a lower degree of aeration within the main tumor lession, as well as slightly increased dimensions of the satellite nodular formations. Therefore, I wonder to which extent the apparent arrest of tumor is indeed an achievement of that treatment or mainly a manifestation of the slow growing nature of the disease.
 
A2) At any rate, I understand from the current medical report that the patient's persistent cough, which seems to be the bothering and most characteristic symptom of her disease, has not been alleviated under treatment with Alimta, thus failing to achieve at least a satisfactory clinical benefit.
 
A3) Furthermore, Alimta would seem to contribute to the patient's untoward reactions such as weakness and nausea up to vomiting, hence deteriorating her quality of life.
 
A4) Therefore, I would agree with the family's question regarding the benefit of further treatment with Alimta and I would not recommend that treatment any more.
 
B) Further treatment options:
B1) The 111In-pentreotide scan dated 7.2008 showed that the patient's tumor is avid to labelled somatostatin analogues. This tumor characteristic would offer her the possibility of a new type of therapy, namely with somatostatin receptor targeted radionuclide therapy. I would, therefore, recommend presenting her medical data to members of a team specialized in that treatment modality, asking whether she might be eligible for treatment. It should be taken in consideration that such a treatment has been reported to be effective in a high percentage of treated patients, especially in terms of palliation. On the other hand, it bears the risk for certain complications, especially correlated with larger tumor size which requires higher doses of radioactive material. Therefore, a preliminary evaluation of the specific case should be conducted by the experienced team as part of the treatment strategy planning.
 
As already mentioned in my previous opinion from May 2008, I recommend that for that purpose you contact either
-       Mueller-Brand J., in the Institute of Nuclear Medicine, University Hospital, University of Basel, Basel, Switzerland.
-        
B2) Only if and when the above mentioned treatment option is exhausted I would consider the less specific modality of another chemotherapy regimen, taking in consideration the corresponding toxicity profile.
 
B3) In case that bothering/exhausting cough represents a limiting factor for the patient's quality of life, and that this is not alleviated by further chemotherapy, there will be place for palliative external irradiation. Optimally, and provided that it is found feasible through bronchoscopy, this should be combined with endobronchial High Dose Rate (HDR) brachitherapy by radioactive seeds.
In addition, low doses of cisplatin should be considered as a "radiosensitizer" along irradiation, either by the daily or by the weekly regimen.

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