Question 1: Compared to the disease status prior to the preparative regimen what was the best response since the date of the last report? (Include response to any post-HSCT treatment planned as of day 0)
This section collects the data known as ‘best response to infusion.’ The purpose of this section is to report the recipient’s best response to the planned course of the infusion. This includes response to any therapy given for post-infusion maintenance, prior to progression (if applicable), but does not include response to treatment given for decreased / loss of chimerism, consolidation, measurable residual disease (MRD), persistent disease, or progressive / relapsed disease.
If the recipient receives consolidation therapy or therapy for MRD, decreased / loss of chimerism, persistent disease, or progressive / relapsed disease, the response to that additional therapy should not be reported in this section. The best response prior to the therapy should be reported. For subsequent reporting periods where the best response prior to the start of unplanned therapy was reported, continue to report the best response captured in the previous reporting period and select Date previously reported when reporting the best response assessment date below.
If the disease status was not assessed at any time in the reporting period, select Unknown. This option should be used sparingly and only when there is no information to determine if disease assessments (i.e., biopsies, scans, labs, etc.) were performed in the reporting period.
Review the reporting examples below for more information.
Questions 2 – 17: Specify the site(s) of persistent tumor
If the best response to infusion is reported as either Partial response, Stable disease, or Progressive disease, indicate if tumor(s) persisted at each site at the time when the best response occurred.
If a tumor persisted at a site not listed, indicate Yes, for Other site and specify the anatomical location.
If it is not known if a tumor persisted at each site at the time of the best response, select No.
Question 18: Specify the date best response was determined
Report the date the best response was established. This should be the earliest date when all international working group criteria for the response reported above were met. If the exact date is not known, use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
If the best response is the same as the pre-infusion disease status, report the date of the first assessment(s) that confirmed the ongoing disease status post-infusion.
Check Previously reported, if the date was already reported on a previous form. This option is not applicable on the day 100 follow-up form.
Reporting Examples
- Example 1: A recipient receives a transplant on 1/1/2015 for neuroblastoma, the pre-infusion disease status is complete remission.
- Day 100 reporting period: During the reporting period, the recipient had radiologic testing performed 3/12/2015 which confirmed the recipient to be in continued complete remission. The 100-day date of contact is 4/15/2015. In this instance, the best response to infusion should be reported as Complete remission on the 100 Day Follow-Up form, with the date best response determined of 3/12/2015 (date of labs / assessments first confirming a continued CR).
- Six-month reporting period: In this reporting period, the recipient relapsed; however, the best response to infusion will still be reported as Complete remission, with the date best response determined as Previously reported. This will be reported in the six-month reporting period and for all subsequent reporting periods. Refer to Table 1 below for further clarification.
Table 1. Reporting Example 1
| Reporting Period | Disease Status | Best Response | Date Best Response Determined |
|---|---|---|---|
| Pre-Infusion | CR | —- | —- |
| 100-Day Reporting Period | CR | CR | 3/12/2015 (date of labs / assessments first confirmed continued CR |
| 6-Month Reporting Period | Relapse | CR | Previously reported |
| 1-Year Reporting Period | CR | CR | Previously reported |
- Example 2: A recipient receives a transplant on 2/5/2015 for neuroblastoma, the pre-infusion disease status is partial remission.
- Day 100 reporting period: During the reporting period the recipient maintained a partial remission, confirmed with a scan performed on 4/1/2015. The 100-day date of contact is 4/22/2015. Report the best response to infusion as Partial remission, with a date best response determined of 4/1/2015 (date of labs/assessments first confirming a continued PR).
- Six-month reporting period: In this reporting period, the recipient progressed and treatment started on 6/1/2015. Continue to report the best response to infusion as Partial remission with the date of best response determined as Previously reported.
- One-year reporting period: In this reporting period, the recipient achieved a complete remission; however, continue to report the best response to infusion as Partial remission with the date of best response determined as Previously reported. The best response to infusion (partial remission) occurred during the 100-day reporting period and response to unplanned therapy is not captured within the best response to infusion data fields. See Table 2 below for further clarification.
Table 2. Reporting Example 2
| Reporting Period | Disease Status | Best Response | Date Best Response Determined |
|---|---|---|---|
| Pre-Infusion | PR | —- | —- |
| 100-Day Reporting Period | PR | PR | 4/1/2015 (date of labs / assessments first confirmed continue PR |
| 6-Month Reporting Period | Disease Progression | PR | Previously reported |
| 1-Year Reporting Period | CR | PR | Previously reported |
Disease Assessments at Time of Best Response
For reporting purposes, the definition of “at the time of best response” depends on the reporting period, see Table 3. below. Only consider assessments with samples collected within the time window which corresponds to the follow-up form being completed. Do not report the assessment if it was performed during the reporting period, but the sample were not collected within the indicated time window.
Table 3. Disease Assessment Time Windows
| Follow-Up Form | Approximate Time Window |
| 100 Day | + / – 15 days of date of best response |
| 6 Month | + / – 15 days of date of best response |
| Annual | + / – 30 days of date of best response |
Question 19: Were tumor markers evaluated for the best response post-HSCT determination?
Tumor markers, also known as biomarkers, are substances produced by cancer tissue or by the body in response to cancer at higher-than-normal levels. In certain situations, these substances can be used to detect and monitor disease due to their elevated presence in blood, urine, and/or tissue. The labs listed below have been identified as potential tumor markers for neuroblastoma.
Specify if any of the tumor markers listed below were assessed at the time of the best response.
- Homovanillic acid (HVA): Catecholamines (e.g. epinephrine/adrenaline) are secreted as hormones from the adrenal medulla. Neuroblastomas typically produce excessive levels of these catecholamines. After catecholamines are secreted they are broken down into metabolites including Homovanillic acid (HVA) and Vanillylmandelic acid (VMA). Both HVA and VMA are excreted in the urine. As a result, elevated levels of HVA and VMA detected by urinary analysis can be indicative of neuroblastoma.
- Neuron specific enolase (NSE): A glycolytic enzyme (enolase) specific to neuronal-type tissues. NSE may be excessively expressed by neuroblastomas and indicative of disease.
- Serum ferritin: Ferritin is a blood protein that contains iron. A ferritin level indicates how much iron a person’s body is storing. If the ferritin level is lower than normal, it indicates the body’s iron stores are low (iron deficiency). If the ferritin level is higher than normal it could indicate hemochromatosis, a condition that causes the body to store too much iron. Other causes of an elevated ferritin level include liver disease, acute and chronic inflammatory conditions, malignancy (neuroblastoma) to name a few.
- Vanillylmandelic acid (VMA): Both HVA and VMA are excreted in the urine. As a result, elevated levels of HVA and VMA detected by urinary analysis can be indicative of neuroblastoma.
- Other tumor marker analysis: Examples of other tumor marker testing can include Chromogranin A (CgA) or Neuropeptide Y (NpY).
If none of the markers listed were assessed at the time of the best response or unknown if assessed, select No.
Questions 20 – 34: Specify the following tumor marker analyses performed
For each tumor marker, indicate if it was analyzed at the time of the best response to infusion. If analyzed, select Known, specify the value and the sample collection date (i.e., the date of best response determination). If an Other tumor marker analysis was completed, specify the tumor marker and units of measurement in addition to the value. If the analysis was not performed or unknown if performed at the time of the best response, select Not known.
Question 35: Was the recipient given planned therapy per protocol post-HSCT treatment for neuroblastoma?
Specify if planned therapy per the protocol was administered during the current reporting period. This includes any treatment administered for reasons other than relapse, progression, persistent disease or measurable residual disease (MRD) identified post-infusion.
If planned therapy was not administered per protocol during the current reporting period or it is unknown if given, select No.
Question 36: Was radiotherapy given?
Radiation therapy utilizes high-energy radiation to kill cancer cells. Indicate whether radiotherapy was given as planned post-infusion therapy per protocol during the current reporting period. If radiotherapy was not used or unknown if radiotherapy was given in the reporting period as part of the planned therapy per protocol, select No.
Questions 37 – 41: Specify the site(s) of radiotherapy
For each site, indicate if radiation therapy was given. If the site of radiotherapy is not listed, select Yes for Other site and specify.
Additionally, report the date when the planned post-infusion radiotherapy began. If multiple sites received radiotherapy, report the first date when radiation was administered in the current reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 42: Number of fractions given
Specify the total number of fractions (treatments) given in the current reporting period. If radiation was administered to multiple sites, report the number of fractions given for the first site during the reporting period.
Question 43: Dose per fraction
Specify the dose per fraction in centigrays (cGy / rads) given in the current reporting period. If radiation was administered to multiple sites, report the dose per fraction of the first site during the reporting period.
Question 44: Was MIBG given?
Meta-iodobenzylguanidine (MIBG) is a radioisotope that is readily absorbed by neuroblastoma cells, preferentially concentrating in areas of disease. At lower doses, MIBG can be used for imaging purposes. At higher doses, MIBG provides selective antitumor radiotherapy.
Indicate whether MIBG was given as planned post-infusion therapy per protocol during the current reporting period. If MIBG was not used or unknown if MIBG was given in the reporting period as part of the planned therapy per protocol, select No.
Questions 45 – 48: Specify the radioisotope given
Specify the radioisotope administered during the current reporting period. If a radioisotope other than 131 I-MIBG was given, select Yes for Other and specify the radioisotope type.
- 131 I-MIBG: Iodine-131 meta-iodobenzylguanidine (I-131 MIBG), commonly known as Azedra is a radiopharmaceutical used for treating certain types of neuroendocrine tumors, including neuroblastomas.
- Other: Targeted radiotherapy such as peptide receptor radionuclide therapy (PRRT).
Additionally, report the start date of MIBG treatment given in the reporting period. If multiple MIBG therapies were given, report the start date of the first MIBG treatment administered in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 49: Were retinoids given?
Retinoids are vitamin A derivatives that can affect cellular function. Studies have shown that retinoid therapy can result in an antitumor effect.
Indicate if retinoids were given as planned post-infusion therapy per protocol during the current reporting period. If retinoids were not used or unknown if retinoids were given in the reporting period as part of the planned therapy per protocol, select No.
Questions 50 – 53: Specify the retinoids given
Specify the retinoid(s) administered during the current reporting period. If a retinoid other than isotretinoin was given, select Yes for Other and specify the retinoid type. Report the generic name and not the brand name.
- Isotretinoin:13-cis-retinoic acid (Isotretinoin) is a retinoid that has been shown to improve survival for high risk neuroblastoma.
- Other: Other types of retinoids given to treat neuroblastoma include N-4-hydroxyphenyl retinamide (Fenretinide),
Additionally, report the start date when the retinoid was given in the reporting period. If multiple retinoids were given, report the start date of the first retinoid administered in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 54: Was immunotherapy given?
Immunotherapy is typically given to stimulate the body’s own immune system to detect and destroy cancer cells.
Indicate if immunotherapy was given as planned post-infusion therapy per protocol during the current reporting period. If immunotherapy was not used or unknown if immunotherapy was given in the reporting period as part of the planned therapy per protocol, select No.
Questions 55 – 60: Specify the drug(s) given
Specify the immunotherapy drug(s) administered during the current reporting period. If an immunotherapy was given but is not listed as an option, select Yes for Other and specify the immunotherapy type. Report the generic name and not the brand name.
- α – interferon: Interferon alfa is a cytokine. Common names include: Intron® A (interferon alfa-2b), Roferon®-A (interferon alfa-2a).
- Anti-GD2 antibody CH14.18: Anti-GD2 antibody ch14.18/CHO (dinutuximab beta) is a chimeric monoclonal antibody.
- Interleukin-2 (IL-2): Interleukin-2 is s a cytokine. Common names include: Aldesleukin and PROLEUKIN®.
- Other: Other types of immunotherapies given to treat neuroblastoma include Granulocyte macrophage colony-stimulating factor (GM-CSF).
Additionally, report the start date when the immunotherapy was given in the reporting period. If multiple immunotherapies were given, report the start date of the first immunotherapy administered in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 61: Was chemotherapy given?
Indicate if chemotherapy was given as planned post-infusion therapy per protocol during the current reporting period. If chemotherapy was not used or unknown if chemotherapy was given in the reporting period as part of the planned therapy per protocol, select No.
Questions 62 – 73: Specify the chemotherapy agent(s) given
Specify the chemotherapy agent(s) administered during the current reporting period. If a chemotherapy agent was given but is not listed as an option, select Yes for Other and specify the chemotherapy type. Report the generic name and not the brand name.
Additionally, report the start date when chemotherapy began in the reporting period. If multiple chemotherapies were given, report the start date of the first chemotherapy administered in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Questions 74 – 76: Was other treatment given?
Specify if treatment other than radiotherapy, MIBG, retinoids, immunotherapy, or chemotherapy was given as planned post-infusion therapy per protocol for neuroblastoma in the current reporting period. Examples of other therapy may include intrathecal therapy or surgery.
If Yes, specify the type of therapy and the start date when therapy began in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 77: Did the neuroblastoma recur or progress since the date of the last report?
Indicate if the neuroblastoma recurred or progressed during the current reporting period. Refer to the Neuroblastoma Response Criteria section of the Forms Instruction Manual.
If relapse / progression did not occur in the reporting period or unknown if it occurred, select No.
Questions 78 – 106: Specify the known site(s) of disease progression / recurrence
Specify the site(s) of disease progression / recurrent and indicate the first date of recurrence / progression in the current reporting period. Enter the date the sample was collected for pathological and laboratory evaluation or enter the date the imaging took place. If the physician determined evidence of disease recurrence or progression in a clinical assessment during an office visit, report the date of the office visit.
If disease progression or recurrence occurred at a site not listed, select Yes for Other site and specify the other site in addition to the progression / recurrence date.
If disease progression or recurrence did not occur at the site or it unknown if it occurred, select No.
If the exact date is not known, use the process for reporting estimated dates as described in the General Instructions Guidelines for Completing Forms.
Questions 107 – 115: Specify the methods used to examine sites of disease recurrence / persistence / progression
Specify the methods used to examine the sites of possible disease recurrence, persistence, and / or progression. If the method was performed in the current reporting period, report Yes and specify if the assessment was Positive or Negative for disease recurrence / progression or persistence of disease.
If a method was used to examine sites of possible disease recurrence / persistence / progression in the current reporting period is not listed as an option, report Yes for Other method and specify the method in addition to reporting the results. Examples of other methods include laboratory testing such as blood and urine tests (e.g., HMA, VMA) for neuroblastoma.
Question 116: Was the recipient given treatment for post-HSCT persistent, progressive or recurrent disease since the date of the last report?
Indicate whether the recipient received therapy in the current reporting period for persistent, progressive, or recurrent disease, including measurable residual disease (MRD).
If therapy for persistent, progressive, or recurrent disease was not given or unknown if given, report No or Unknown, respectively.
Question 117: Was radiotherapy given?
Radiation therapy utilizes high-energy radiation to kill cancer cells. Indicate whether radiotherapy was given as treatment for post-infusion persistent, progressive, or recurrent disease, including MRD, in the current reporting period. If radiotherapy was not used or unknown if radiotherapy was given in the reporting period, select No.
Questions 118 – 122: Specify the site(s) of radiotherapy
For each site, indicate if radiation therapy was given. If the site of radiotherapy is not listed, select Yes for Other site and specify.
Additionally, report the date when radiotherapy began. If multiple sites received radiotherapy, report the first date when radiation was administered in the current reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 123: Number of fractions given
Specify the total number of fractions (treatments) given in the current reporting period. If radiation was administered to multiple sites, report the number of fractions for the first site during the reporting period.
Question 124: Dose per fraction
Specify the dose per fraction in centigrays (cGy / rads) given in the current reporting period. If radiation was administered to multiple sites, report the dose per fraction of the first site during the reporting period.
Question 125: Was MIBG given?
Meta-iodobenzylguanidine (MIBG) is a radioisotope that is readily absorbed by neuroblastoma cells, preferentially concentrating in areas of disease. At lower doses, MIBG can be used for imaging purposes. At higher doses, MIBG provides selective antitumor radiotherapy.
Indicate whether MIBG was given as post-infusion therapy for persistent, progressive, or recurrent disease, including MRD, in the current reporting period. If MIBG was not used or unknown if MIBG was given in the reporting period, select No.
Questions 126 – 129: Specify the radioisotope given
Specify the radioisotope administered during the current reporting period. If a radioisotope other than 131 I-MIBG was given, select Yes for Other and specify the radioisotope type.
- 131 I-MIBG: Iodine-131 meta-iodobenzylguanidine (I-131 MIBG), commonly known as Azedra is a radiopharmaceutical used for treating certain types of neuroendocrine tumors, including neuroblastomas.
- Other: Targeted radiotherapy such as peptide receptor radionuclide therapy (PRRT).
Additionally, report the start date of MIBG treatment given in the reporting period. If multiple MIBG therapies were given, report the start date of the first MIBG treatment administered in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 130: Were retinoids given?
Retinoids are vitamin A derivatives that can affect cellular function. Studies have shown that retinoid therapy can result in an antitumor effect.
Indicate if retinoids were given as post-infusion therapy for persistent, progressive, or recurrent disease, including MRD, in the current reporting period. If retinoids were not used or unknown if retinoids were given in the reporting period, select No.
Questions 131 – 134: Specify the retinoids given
Specify the retinoid(s) administered during the current reporting period. If a retinoid other than isotretinoin was given, select Yes for Other and specify the retinoid type. Report the generic name and not the brand name.
- Isotretinoin: 13-cis-retinoic acid (Isotretinoin) is a retinoid that has been shown to improve survival for high risk neuroblastoma.
- Other: Other types of retinoids given to treat given to treat neuroblastoma include N-4-hydroxyphenyl retinamide (Fenretinide).
Additionally, report the start date when the retinoid was given in the reporting period. If multiple retinoids were given, report the start date of the first retinoid administered in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 135: Was immunotherapy given?
Immunotherapy is typically given to stimulate the body’s own immune system to detect and destroy cancer cells.
Indicate if immunotherapy was given as post-infusion therapy for persistent, progressive, or recurrent disease, including MRD, in the current reporting period. If immunotherapy was not used or unknown if immunotherapy was given in the reporting period, select No.
Questions 136 – 141: Specify the drug(s) given
Specify the immunotherapy drug(s) administered during the current reporting period. If an immunotherapy was given but is not listed as an option, select Yes for Other and specify the immunotherapy type. Report the generic name and not the brand name.
- α – interferon: Interferon alfa is a cytokine. Common names include: Intron® A (interferon alfa-2b), Roferon®-A (interferon alfa-2a).
- Anti-GD2 antibody CH14.18: Anti-GD2 antibody ch14.18/CHO (dinutuximab beta) is a chimeric monoclonal antibody.
- Interleukin-2 (IL-2): Interleukin-2 is s a cytokine. Common names include: Aldesleukin and PROLEUKIN®.
- Other: Other types of immunotherapies given to treat neuroblastoma include Granulocyte macrophage colony-stimulating factor (GM-CSF).
Additionally, report the start date when the immunotherapy was given in the reporting period. If multiple immunotherapies were given, report the start date of the first immunotherapy administered in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 142: Was chemotherapy given?
If the recipient received chemotherapy as post-infusion therapy for persistent, progressive, or recurrent disease, including MRD, in the current reporting period. If chemotherapy was not used or unknown if chemotherapy was given in the reporting period, select No.
Questions 143 – 154: Specify the treatment(s) given
Specify the chemotherapy agent(s) administered during the current reporting period. If a chemotherapy agent was given but is not listed as an option, select Yes for Other and specify the chemotherapy type. Report the generic name and not the brand name.
Additionally, report the start date when chemotherapy began in the reporting period. If multiple chemotherapies were given, report the start date of the first chemotherapy administered in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Questions 155 – 157: Was other treatment given
Specify if a treatment other than radiotherapy, MIBG, retinoids, immunotherapy, or chemotherapy was given as post-infusion therapy for persistent, progressive, or recurrent disease, including MRD, in the current reporting period. Examples may include intrathecal therapy or surgery.
If Yes, specify the type of therapy and the start date when therapy began in the reporting period.
If the start date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Question 158: What is the current disease status?
Report the current disease status as of the last evaluation in the reporting period using the international working group criteria provided in the Neuroblastoma Response Criteria of the Forms Instructions Manual. Molecular or cytogenetic evidence of disease should not be considered when determining the current disease status.
The center does not need to repeat all disease-specific assessments (biopsies, scans, labs) each reporting period in order to complete current disease status data fields. Once a particular disease status is achieved, the center can continue reporting that disease status (based on labs / clinical assessments) until there is evidence of relapse / progression. If a disease-specific assessment did not occur during this time period (i.e., a biopsy or scan), report the current status using the date of a disease related assessment (i.e., clinical assessments, labs, etc.).
If the disease status was not assessed at any time in the reporting period, select Unknown. This option should be used sparingly and only when there is no information to determine if disease assessments (i.e., biopsies, scans, labs, etc.) were performed in the reporting period.
Question 159: Specify the date the current disease status was determined
Report the date of the pathological evaluation or radiographic assessment (e.g., bone marrow biopsy, CT scan, etc.). If no pathologic / radiographic evaluation was performed in the reporting period, report the date of blood / serum / urine assessment (e.g., CBC, peripheral blood smear). Enter the sample collection date. If a radiological assessment (e.g., X-ray, CT scan, MRI scan, PET scan) was performed to assess disease response, enter the date the imaging took place. If no pathological, radiographic, or laboratory assessment was performed to evaluate the disease status, report the office visit in which the physician clinically assessed the recipient’s response.
If the date is partially known (i.e., the recipient started treatment in mid- July 2010), use the process described for reporting partial or unknown dates in General Instructions, Guidelines for Completing Forms.
Section Updates
| Question Number | Date of Change | Add/Remove/Modify | Description | Reasoning (if applicable) |
|---|---|---|---|---|
| . | . | . | . | . |
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