Chemotherapy Response and Definitive or 2nd Look Surgery

Experience suggests that response to chemotherapy is prompt, and maximum response occurs after 2 - 4 courses of therapy. If the patient had a partial resection as initial surgery, we recommend repeat (2nd look) surgery and an attempt at complete resection (with sampling of resection margins) after 2 - 4 courses (approximately 10 - 12 weeks) of IVADo therapy. Also, in the neo-adjuvant setting, we recommend surgery and an attempt at complete resection (with sampling of resection margins) after 2 - 4 courses (approximately 10 - 12 weeks) of the therapy.

Chest radiographs and CT scans should be done after each course to assess response and/or continuing response. If there is no response after 2 courses, maximal surgery should be attempted, and a decision to stay with the same chemotherapy would be difficult and would depend on whether there is very extensive (nearly complete) necrosis pathologically. If there is a complete radiographic response to chemotherapy, as has been rarely reported, we recommend surgery to resect any observable remainder of the primary site.

After definitive surgery and assuming no evidence of recurrence, chemotherapy should continue for the planned IVADo courses. Use of radiation is discussed below.

Intracavitary Chemotherapy or Radiotherapy

Types II and III PPB are often found at surgery to be extremely friable, hemorrhagic, and/or “necrotic”. Resection may be morselized or piecemeal and “spillage” is common. Whether this phenomenon contributes to recurrence is not known, but in Wilms’ tumor treatment, spillage leads to more intensive therapy and to the use of abdominal radiation.

Clinicians facing gross PPB spillage may want to consider intracavitary chemotherapy. Intracavitary therapy, especially cis-platinum, has been used quite extensively in medical oncology for pleural and peritoneal metastatic disease, and the doses and toxicities are well described [see Literature Sources, Boyer 1995, Brenner 1986, Markman 2001]. Intracavitary (“topical”) therapy is useful only for small-volume surface disease: nodules less than 0.5 to 1.0 cm diameter [Markman].

Intracavitary cis-platinum has been reported in three cases of PPB [see Literature Sources, Boyer et al and Yang et al]. In one case (Type II), a recurrent nodule in the pleura was excised, and the patient then received 200 mg/M2 cis-platinum intrathoracically, 4200 cGy radiation, and systemic platinum and doxorubicin. The child is well 15 years later. In the second case (Type II), the child received intracavitary platinum at diagnosis for spillage, aggressive additional chemotherapy and is NED 9 years later [Boyer + unpublished data]. In the third case (Type II), a 29-month old had extensive disease in the right upper lobe and a pleural nodule. After lobectomy and nodulectomy, the child was given 10 mg cis-platinum intrathoracically in the operating room before closure. Post-operative systemic chemotherapy (VAC) was given for 3 months. The child was disease free at 3 years [Yang].

Inracavitary ³²P, along with other therapies, has also been given for pleural disease in two Registry cases. One child received 32P at diagnosis for gross tumor spillage. He also received aggressive additional chemotherapy and thoracic radiation; at last follow up he was NED 48 months from diagnosis. The other child received 32P five months after diagnosis for recurrent pleural disease; he died 8 months later of CNS disease. Intraoperative brachytherapy has also been reported for control of residual intrathoracic disease [Bibliography, Nag et al] and in one case of intracerebral disease).

Chemotherapy for Recurrent PPB

Therapy for PPB that recurs after chemotherapy must be highly individualized. HDCT + ASCR has been attempted in several children and is summarized in the HDCT + ASCR Table. This table abstracts several cases treated by high-dose chemotherapy and ASCR. Some of these children have survived longer than 36 months, suggesting that ASCR appears to offer some promise from these small numbers.

Several children appear to have been successfully treated for CNS recurrence. Clinicians are encouraged to contact the Registry for data on treatment and outcome in CNS recurrence. A child in the literature was treated with high-dose cyclophosphamide and whole brain radiation (3000 cGy in 12 doses) [see Literature Sources; focus: survival of CNS metastasis]

Radiation Therapy

There have been no studies addressing the necessity for radiation therapy for PPB. In the published Registry series of 50 cases, statistical benefit to the use of radiation was not shown. Of the 16 children with Type III disease who received radiation therapy, 8 developed recurrences and 5 of those recurrences were in the radiation field.

Patients with Types II and III disease have been cured after surgery and chemotherapy, with and without radiation. The amount of radiation to the entire (or hemi) thorax is limited to 1200 - 1400 cGy due to lung toxicity. Use of anthracycline also poses limits.

The treating institution must individualize the use of radiation in PPB. The Registry recommends that radiation be strongly considered for sites of known residual disease after surgery, whether primary ablative surgery or surgery following neo-adjuvant chemotherapy. Doses given to PPB patients have been in the range of 1200 - 1400 cGy to a hemithorax with focal fields receiving 3000 - 5000 cGy (see Registry Publications: Priest et al 1997). If radiation is to be used, it is not known when it should be given. If radiation therapy is to be used during chemotherapy, doxorubicin and actinomycin should be omitted during the radiation. If radiation to the mediastinum is to be used, doxorubicin cumulative total doses are adjusted as discussed above.

Intracavitary ³²P has also been given for pleural disease in two Registry cases along with other therapies two Registry cases along with other therapies. One child received 32P at diagnosis for gross tumor spillage. He also received aggressive additional chemotherapy and thoracic radiation; he was NED 48 months from diagnosis. The other child received 32P five months after diagnosis for recurrent pleural disease; he died 8 months later of CNS disease.

Radiation therapy has commonly been used after surgery for CNS (cerebral parenchyma) metastasis.