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Type I PPB Treatment Recommendations
PPB Registry Treatment Recommendations: Local physicians have complete responsibility for and autonomy in selecting and managing treatments for their PPB patients.
The PPB Registry offers the following treatment recommendations for Type I PPB based on anecdotal Registry and literature information discussed below. Because of the rarity of PPB, there have been no prospective treatment trials. The Registry does not consider these suggestions a prospective treatment trial.
The PPB Registry is not a part of, nor funded by, any cooperative oncology group, although Children’s Oncology Group Rare Tumor Sub-Committee recognizes the Registry as a major collection of PPB cases.
Surgery - Type I PPB
In many Type I cases, the indication for surgery is cystic lung disease and there is little pre-operative concern about a malignancy. The clues to a malignant process would be bilateral cystic lung disease*, an extensive multilocular cyst*, or any family history of lung cysts, cystic nephroma, or childhood cancer. See Constitutional Disease: Lung Cysts and More and Familial Disease and Dysplastic and Neoplastic Conditions in PPB Patients and their Families. (*Bilaterality rarely occurs also in benign cystic lung malformations.)
Type I disease is entirely cystic and may be unilocular or multilocular, unifocal or multifocal, and unilateral or bilateral. Every attempt should be made to remove completely all cystic remnants, but the Registry has seen cases in which not all cysts in a Type I patient show the changes of Type I PPB. Therefore, the Registry understands that in children with widespread cystic lung changes, not all the cysts can or should be removed. Type I recurrences frequently progress to more serious Type II or III disease (see Prognosis for PPB).
Chemotherapy - Type I PPB
Clinicians are encouraged to contact the Registry for updates on the following recommendations and the data on which they are based. Please see also the series published by the PPB Registry on Type I PPB: Priest et al Type I pleuropulmonary blastoma. J Clin Oncol 2006; 24:4492-8.
This paper discusses 38 Type I PPB cases and includes literature and Registry cases. In this analysis, there is a suggestion that adjuvant chemotherapy improves outcome in Type I PPB.
As of mid-2009, the following is PPB Registry data on 58 Registry-reviewed Type I PPB cases (no literature cases):
International PPB Registry Type I PPB (n = 58)
(This data is published only in part; citation noted above)
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Surgery without Adjuvant Chemorx |
Surgery plus Adjuvant Chemorx |
| Total Cases |
n = 27 |
n = 31 |
| No Recurrence |
n = 18 |
n = 30 |
Recurrence
|
n = 9*
Outcome:
3 DOD
6 NED |
n = 1**
Outcome:
1 DOD |
*7 of 9 recurrences were Type II or III PPB (time to recurrence from initial diagnosis: 3, 6, 12, 23, 25, 30, and 37 months); 2 of 9 recurrences were Type I PPB (time to recurrence 3 and 7 months).
** Type III at recurrence, 54 months after diagnosis.
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When deciding whether to use chemotherapy for Type I PPB, clinicians treating children with Type I PPB should combine information in the 2006 JCO paper with the Registry-only up-dated data given here.
Worldwide, there is not a concensus on whether children with Type I PPB should receive adjuvant chemotherapy. In general, the PPB Registry recommends VAC-type chemotherapy for Type I PPB. Alternatively, aggressive follow-up of surgery-only Type I PPB patients might allow recurrences to be identified while still Type I disease, compelling additional surgery and chemotherapy at that time. A recurrence of Type I PPB as Type II or III disease markedly reduces the prognosis for the child. The Registry recommends chemotherapy for three reasons:
- the tendency forType I PPB to progressed at recurrence to Type II or III, which are poorly salvaged.
- the Wilms tumor experience with no chemotherapy for Stage I disease, which resulted in a 13% recurrence rate (with better salvage rates than appear to apply to PPB)
- the general tolerability of VAC therapy
Regardless of whether the child receives chemotherapy for Type I, the Registry recommends diligent surveillance of Type I patients until they reach 60 months of age, because cysts becoming PPBs and Type I recurrences cluster in the 3rd and 4th years of life. (see Recommendations - Surveillance)
PPB Registry Recommendations for Chemotherapy for Type I PPB: (Click here to download this schema and roadmaps).
Week of therapy: |
0 |
1 |
2 |
3 |
4 |
5 |
6 |
7 |
8 |
9 |
10 |
11 |
12 |
Vincristine: |
V |
V |
V |
V |
V |
V |
V |
V |
V |
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V |
Actinomycin D*: |
A* |
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A* |
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A* |
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A* |
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A* |
Cyclophosphamide: |
C |
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C |
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C |
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C |
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MESNA: |
M |
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M |
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M |
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M |
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Week of therapy: |
13 |
14 |
15 |
16 |
17 |
18 |
19 |
20 |
21 |
22 |
23 |
Vincristine: |
V |
V |
V |
V |
V |
V |
V |
V |
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Actinomycin D*: |
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A* |
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A* |
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A* |
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Cyclophosphamide: |
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MESNA: |
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*Omit Actinomycin D if radiation therapy is used during this course
Chemotherapy, MESNA, and G-CSF Dose Guidelines for Type I PPB
Patients will be dosed according to their age at the time of scheduled treatment |
| Age |
VCR Dose |
AMD Dose |
CPM Dose |
Adjustments |
| ≥3 yrs |
1.5 mg/m2 IV push (max dose 2.0 mg) |
0.045 mg/kg one dose (max dose 2.5 mg) |
1.2 gm/m2 IV as 1 hr infusion with IV fluids and MESNA***
|
Omit AMD if radiation therapy is used |
< 3 yrs
≥1 yr |
0.05 mg/kg IV push (max dose 2.0 mg). |
0.045 mg/kg one dose (max dose 2.5 mg) |
40 mg/kg/dose IV as 1 hr infusion with IV fluids and MESNA***
|
Omit AMD if radiation therapy is used |
| < 1 yr |
0.025 mg/kg IV push |
0.025 mg/kg one dose |
40 mg/kg IV as 1 hr infusion with IV fluids and MESNA***
|
Omit AMD if radiation therapy is used |
*** MESNA doses: < 3 yr: 8 mg/kg/dose X 3 doses: dose 1 with CPM over 1 hour; doses 2 and 3 IV push over 3 – 5 min at hours 4 and 8.
> 3 yr: 240 mg/m2/dose X 3 doses: dose 1 with CPM over 1 hour; doses 2 and 3 IV push over 3 – 5 min at hours 4 and 8.
G-CSF doses (if G-CSF used; see * above), all ages: 5 mcg/kg/day s.c. Q.D. starting day 1, 24 hrs after VAC, continuing daily for 10 days or until nadir has passed and ANC > 2000/microliter. OMIT in Weeks 21, 33, and 45 of therapy. |
Details of administering chemotherapy and monitoring toxicity are not discussed here but should follow routine practices in pediatric oncology.
Alternative to Adjuvant Chemotherapy for Type I PPB
Please see also published PPB Registry series on Type I PPB: Priest et al Type I pleuropulmonary blastoma. J Clin Oncol 2006; 24:4492-8.
Perhaps an alternative to adjuvant chemotherapy in the child with completely resected Type I PPB is monitoring for early detection of recurrence. In three recent Registry cases, physicians have used a close surveillance strategy to modulate therapy for Type I PPB. The ultimate outcome in these children is not yet known. Examples are as follows: In one child, seven months after Type I PPB diagnosis, remaining cysts enlarged, were resected and showed Type I PPB; chemotherapy was then initiated. In another child, 16 months after Type I diagnosis, remaining cysts enlarged and were resected. Diagnostic features of Type I PPB were not seen in the residual cyst material, and the child continues to be observed without adjuvant chemotherapy. In a third child, 48 weeks of adjuvant chemotherapy was planned following Type I diagnosis. At 28 weeks, enlarging cysts were resected. Compared to the initial specimen, cyst walls showed hyalinized nodules, hemorrhage, abundant macrophages, and rare cartilage nodules with few nodules of primitive cells, consistent with chemotherapy effect. No residual confluent layers of primitive cells (cambium layer) were seen. Based on these findings, the original plan was continued.
A close surveillance schedule for Type I PPB recurrence must recognize that
- the natural history of PPB is cystic Type I PPB in the youngest patients, typically under age 2 years, with progression to solid disease in older children: Type II PPB average age of diagnosis 34 months and Type III PPB average age at diagnosis 44 months. Thus, Type I disease may recur as Type II or III PPB up to the age of about 60 months and rarely later (maximum age observed of a child with cystic lung disease which progressed to PPB was 12 years at progression; maximum age of a child with Type I PPB which recurred was 76 months at recurrence[54 months after PPB Type I diagnosis]),
- PPB recurrence may be fulminant and scans must be at 3-month intervals, and
- CT is the best surveillance modality.
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