Localized CPP

Regardless

Watch

No progression

Watch and wait

Regardless

Watch and wait

Local tumor progression

2nd OP if second resection is completed, then treat like first resection. If there is residual tumor or already at third resection, then move down in algorithm; treat as if localized APP with residual tumor (localized or metastatic)

Regardless

Watch

Metastatic progression

Move down in algorithm; treat as if localized APP with residual tumor (localized or metastatic)

Metastatic CPP

No

Watch

CCR

Watch and wait

No

Watch

Tumor progression

2nd OP if possible. Start 1st systemic chemotherapy with IT. Reevaluate. Continue 1st ChT if SD or better without XRT; change treatment if progression, single site resect + 2nd ChT, multiple sites <3 years, 2nd ChT, multiple sites >3years CSI followed by 2nd ChT

Yes

1st ChT + ith

CR, PR, SD

Continue ChT +ith; complete protocol; start watch and wait without XRT

Yes

1st ChT + ith

PD single site

If further resection successful, watch and wait. If resection impossible, 2nd ChT 2 cycles. Reevaluate. If PR or CR, continue 2nd ChT. If PD or SD, local XRT and 3rd ChT for >1.5 years and or only 3rd chemo if <1.5 years

Yes

1st ChT + ith

PD multiple sites

>3 years, CSI + 2nd ChT >2.5–3 years, 2nd.ChT +ith, delay CSI, <2.5 years, 2nd ChT+ ith no XRT

No

Watch and wait

CCR

Watch and wait as long as no recurrence

No

Watch and wait

Tumor progression

Consider resecting the tumor. But move on in treatment regardless of success. Start 1st chemotherapy without intrathecal chemotherapy. Follow guidelines as if newly diagnosed APP with residual tumor (one line lower)

Yes

1st ChT

CR

Complete chemotherapy protocol. No XRT. No IT chemo

Yes

1st ChT

PR

Attempt resection again. If resection complete, continue 1st ChT without radiation. If resection incomplete, treat age dependently: <1 year, continue ChT without radiation; 1–1.5 years, continue 1st ChT, give delayed local RT to residual tumor; >1.5 year, give local RT to residual tumor and continue 1st ChT. No IT ChT

Yes

1st ChT

SD

Attempt resection again. Independent of result of resection, treat age dependently: <1 year, continue ChT without radiation; 1–1.5 years, continue 1st ChT, give delayed local RT to residual tumor; >1.5 year, give local RT to residual tumor without delay and continue 1st ChT. No IT ChT

Yes

1st ChT

PD in single site

Attempt resection. <1 year, 2nd ChT no IT, no XRT; 1–1.5 years, 2nd ChT no IT delayed local XRT; >= 1.5 years, local XRT 2nd ChT no IT;

Yes

1st ChT

PD multiple sites

>3 years, CSI + 2nd ChT without IT; >2.5–3 years, 2nd ChT + IT, delayed CSI complete 2nd ChT without IT; <2.5 years, 2.ChT+IT (CSI for third recurrence)

CCR or CR

<2.5 years

Continue 1st CT with IT chemotherapy. Evaluate by the end of the protocol. If there is still no tumor, watch and wait protocol

2.5–3 years

Continue 1st CT with IT. Delay CSI XRT until patient is 3 years old. Finish protocol without IT. Evaluate after 6 cycles. Continue if there is still detectable tumor with less intense treatment and reconsider surgery

>3 years

CSI XRT until patient is 3 years old. Continue 1st ChT without IT. Evaluate after 6 cycles. Continue if there is still detectable tumor with less intense treatment and reconsider surgery

PR or SD

<2.5 years

Consider surgery. Continue 1st CT with IT chemotherapy. Evaluate by the end of the protocol. If there is still no tumor, watch and wait protocol

2.5–3 years

Consider surgery. Continue 1st CT with IT. Delay CSI XRT until patient is 3 years old. Finish protocol without IT. Evaluate after 6 cycles. Continue if there is still detectable tumor with less intense treatment and reconsider surgery

>3 years

Consider surgery CSI XRT until patient is 3 years old. Continue 1st ChT without IT. Evaluate after 6 cycles. Continue if there is still detectable tumor with less intense treatment and reconsider surgery

PD in single site

<1

Change treatment to 2nd ChT and 2nd IT. No XRT

1–1.5

Change treatment to 2nd ChT and 2nd IT. Delay local XRT until 1.5 years. Finish 2nd ChT without IT after XRT

1.5–2.5

Change treatment to 2nd ChT; start simultaneously with local XRT. Finish 2nd ChT without IT after XRT

2.5–3

Change treatment to 2nd ChT with 2nd IT. Delay XRT until 3 years; then give CSI. Finish 2nd ChT without IT after XRT

>3

CSI XRT followed by 2nd ChT without IT

PD in multiple sites

<2.5

Change treatment to 2nd ChT and 2nd IT. No XRT

2.5–3

Change treatment to 2nd ChT with IT. Delay XRT until 3 years; then give CSI. Finish 2nd ChT without IT after XRT

>3

CSI XRT followed by 2nd ChT without IT

CCR or CR

<2.5 years

Continue same 1st ChT with IT. No XRT. Reevaluate. Start watch and wait

<2.5–3 years

Continue same 1st ChT with IT. Delay XRT until 3 years old; then give CSI XRT. Finish 1st ChT without further IT. Reevaluate. Start watch and wait

>3 years

CSI XRT followed by same 1st ChT without IT. Evaluate. Watch and wait

PR or SD

<1.5

Reoperate. Continue same 1st ChT with IT until 1.5 years old. Reevaluate. If there is still a residual, give local XRT. Otherwise, just watch and wait

1.5–2.5 years

Reoperate. Continue same 1st ChT with IT for a total of 6 cycles. Local XRT might be delayed but should be given regardless of tumor status

2.5–3 years

Continue same 1st ChT with IT. Delay XRT until 3 years old; then give CSI XRT. Finish 1st ChT without further IT. Reevaluate. Start watch and wait

>3 years

CSI XRT followed by same 1st ChT without IT. Evaluate. Watch and wait

PD single site

<1 years

Consider resection. Change chemotherapy: 2nd ChT with 2nd IT, no XRT

1–1.5 years

Consider resection. Change chemotherapy: 2nd ChT with 2nd IT; delay local XRT until 1.5 years

1.5–2.5 years

Consider resection. Local XRT + changed chemotherapy: 2nd ChT with 2nd IT start simultaneously with XRT

2.5–3

Consider resection. Change chemotherapy: 2nd ChT with 2nd IT; delay XRT until 3 years; then give CSI. Complete protocol after CSI without IT. Might need dose reduction for bone marrow toxicity

>3

Consider resection. CSI XRT, followed by changed chemotherapy: 2nd ChT without IT

PD multiple sites

<2.5 years

Change chemotherapy: 2nd ChT with 2nd IT, no XRT. Reevaluate by the end of the protocol. If there is still tumor, reconsider local therapy or low-intense long-term chemo

2.5–3 years

Change chemotherapy: 2nd ChT with 2nd IT; delay XRT until 3 years; then give CSI. Complete chemotherapy without IT. Might need dose reduction for bone marrow toxicity