Cystic Pleuro-Pulmonary Blastoma – additional opinion

1) Do you agree with the treatment chosen?

Yes, the treatment plan proposed by Dr. Z and his colleagues is a very reasonable one. However, it would be helpful to have some additional details. First, I wonder whether the histologic diagnosis of PPB has been further subclassified. It has been described as a cystic PPB. There are classically 3 subtypes described for PPB: type I: purely cystic; type II: purely solid; and type III: mixed cystic and solid. I suspect from the radiographic description and the child's age that this is a type III (mixed) as the type I, purely cystic lesions tend to occur in younger infants and would often be less extensive. There is some suggestion in the literature that type I lesions are favorable in their prognosis and also that chemotherapy and/or radiation therapy may not be necessary if the tumor can be removed in entirety through surgical resection. One consideration if there is any uncertainty about the histologic subtype would be to send the pathologic materials for outside review. This could be done at our institution (in particular, would recommend Dr. Andrew Rosenberg here at MGH) or by Dr. Louis Dehner, a pathologist at the University of Minnesota who is recognized as an expert in this rare tumor type. I would be happy to help arrange for this to be done if you are interested. Having said this, I do feel that the likelihood clinically is that this is a mixed, type III lesion.

My other question is whether the surgical consultants felt there was any feasibility to resecting the tumor at the time of initial diagnosis. Again, I would speculate given the description of the tumor location and its behavior was that this was not felt to be readily amenable to surgical resection and this is the rationale for starting with chemotherapy and deferring surgery. Generally, the approach has been to remove tumor at the time of diagnosis if possible but there are patients in whom this is not feasible and treatment has been successful with a delayed surgery after some upfront treatment with chemotherapy. In one of the larger published series of PPB patients, Indolfi and colleagues outlined the management and outcome of 11 children, and 3 of these 11 had delayed surgery, 2 of 3 with a good treatment outcome (Indolfi P, Cancer 2000; 89:1396-1401).

As to the question of optimal chemotherapy if this is not a type I, purely cystic tumor that would be amenable to up-front surgical resection, the choice you have proposed is a standard regimen that has been used with some frequency in this disease. Given the relative rarity of PPB, there has not been one gold standard chemotherapy regimen that has been used universally. The regimens generally chosen (VAIA, VAC, and CEVAIE) are typical regimens used for sarcomas of childhood and in particular for rhabdomyosarcoma with which this tumor shares some similarities. VAC has been the U.S. standard regimen for rhabdomyosarcoma and is probably used more often here than VAIA, while VAIA has been a very comparable European standard regimen. Studies in rhabdomyosarcoma comparing these regimens show very similar effectiveness and I think it makes the most sense to choose a good sarcoma regimen as you have done that your group and team are comfortable with.

One additional consideration is whether this child should receive radiation therapy as part of her treatment. This will depend to some extent on whether the tumor can be completely removed with clear surgical margins, in which case radiation may be able to be avoided. There is a suggestion in the literature that there may be a benefit to including local radiotherapy in the overall treatment plan (see Indolfi reference), and I think this should be strongly considered post-operatively, particularly if there is known to be residual tumor left in place. Certainly, radiating the chest of such a young child has significant attendant morbidities, particularly long-term toxicities such as impaired growth of musculoskeletal tissues and adverse effects on cardiac and pulmonary function. The magnitude of these late toxicities depends on the dose used, the size of the field, and also the form of radiation delivered. There may be benefit in terms of the reduction of late toxicities to using proton beam irradiation if this is available. We would certainly consider this form of radiation here but it is available at just a few centers internationally (including our own).

2) Prognosis?

Prognosis depends on histologic subtype and also on extent of disease. Patients with types 2 and 3 PPB as well as those with pleural and/or mediastinal involvement appear to have a worse outcome in the published series (Indolfi reference and Priest JR, Cancer, 1997;80:147-1961). If this is indeed a type 3 with pleural and mediastinal involvement as the description of the imaging studies suggests, the literature suggests that there is about a 40-45% chance of event-free survival and possibly a small number of patients who are successfully retreated after salvage therapy. Certainly, there are long-term survivors of this disease and my recommendation would be to treat this aggressively with a curative intent to include at least chemotherapy and surgery as you have outlined, and possibly also radiation therapy if there is residual disease remaining after surgery.

3) Possible options to the surgical operation?

I would defer this question to my pediatric surgery colleagues. This is difficult to answer without direct review of the imaging studies but my general recommendation would be to undertake whatever aggressive surgery is required to remove as much disease as possible. It would be helpful to know whether the effusion was malignant (positive tumor cells by cytology) or reactive/inflammatory and whether the tumor is felt to be adherent to pleura and mediastinum or nearly abutting these structures. If there were tumor cells in pleural fluid and/or tumor is densely adherent to pleura, consideration may need to be given to pneumonectomy. The decision as to how to approach this surgically will be easier to address once the response to neoadjuvant chemotherapy has been assessed. I would be very happy to review the actual images and also discuss/review the case in a multidisciplinary manner with my radiation oncology and pediatric surgery colleagues for a more detailed opinion on multimodality therapy, including the role of radiotherapy (and possibly protons) and recommendations for surgery.