Appendix

CancerPal©

It is important to realize that CancerPal© remains an experimental tool used strictly for analysis of clinical and laboratory data by cancer researchers, pharmacists or clinical research radiation and medical oncologists. The methods used in designing this tool have been discussed primarily in the references listed below with special attention given to the work of Mehrara et al. PNA, A Limited Liability Corporation, cannot be held responsible for any treatment modifications or recommendations made based on this research tool.

What CancerPal© does

CancerPal© evaluates whether a chemotherapy or targeted therapy should be continued alone, possibly dropped or added to by revealing concealed drug activity causing suppression of the tumor specific growth rate. The app uncovers occult efficacy of drugs by comparing the measured drug-induced tumor size vs. the projected tumor size or projected tumor-marker value that would occur in the absence of any therapy. Sudden changes in tumor growth rate suggesting drug related tumor stimulation or a detrimental, growth-promoting mutation is rapidly identified. CancerPal© may uncover hidden tumor acceleration unexpectedly caused by drugs, immunosuppression or alternative therapies thought to be harmless

CancerPal© uses a tumor's specific growth rate (TSGR) defined as percentage increase in volume per day or percentage increase in the specific tumor marker per day thus avoiding errors inherent in the doubling time calculation which consistently overestimates the growth rate of slowly growing tumors and underestimates the growth rate of rapidly growing tumors.

This app predicts the tumor diameter or tumor marker value at any time in the future assuming constant exponential tumor or tumor marker growth over the period of observation. This, when compared to the actual measured tumor diameter or marker value, identifies tumor response, stability or acceleration. The app predicts a tumor marker or diameter at any time point in the future based on patient-specific tumor kinetics. CancerPal© may quickly alert the clinician of emergence of a mutant, more aggressive, rapidly dividing clone of tumor cells suggesting a review of therapy. Analysis based on continual exponential growth for the relatively short time (several months) in the multi-year history of tumor growth has been found to be more useful for kinetic calculations in spite of some tumors demonstrating Gompertzian growth over the long haul (several years)

Continuous variables for Tumor Response (TR) and Marker Response (MR) allow for quan-titation of drug/biological response modulator effects. Negative values of TR and MR indicate tumor acceleration, values close to or equal to zero indicate lack of response while positive values confirm beneficial tumor response. Responses are numerically quantitated and elusive disease stability may now numerically be defined by a continuous variable. Drugs previously thought to be of no value may be found to induce useful and profound disease stability

The software is helpful for those patients followed by watchful waiting/active surveillance for prostate or any other cancer. Prostate tumors changing biological behavior are immediately identified in a quantitative and objective manner by rapidly uncovering changes in PSA kinetics without the errors inherent in the PSA doubling time (PSA-DT) parameter. The software can help determine whether metastectomy is a reasonable treatment modality for some patients with pulmonary metastasis [83].

CancerPal© uses the exponential growth constant as described by John Spratt to extrapolate backwards to approximate the time of tumor initiation in years based on the rate of growth

Patient data required for analysis

Three dates and three associated measurements of a tumor marker or tumor diameter

• TDx (date at diagnosis + marker value or tumor diameter in cm)

• TPreRx (date of initiation of Rx + marker value or tumor diameter in cm)

• TPostRx (date of measurement of drug effect + tumor marker value or diameter in cm). CancerPal© information output:

• Tumor Specific Volume Growth Rates for two intervals (TSGRj and TSGR2)

• Tumor Marker Specific Growth Rates for two intervals (MSGRj and MSGR2)

• Tumor Specific Growth Rate acceleration and deceleration

• Tumor Volume Doubling Times for two intervals (TVDT)

• Tumor Marker Doubling Time for two intervals (MDT)

• Projected TSGR and MSGR at any user designated time in the future

• Treatment Response as both Tumor Response and Tumor Marker Response, both as continuous numerical values used to quantitate the effect of therapy. Negative numbers reveal growth acceleration; values of zero reveal no effect and positive values indicate varying degrees of therapeutic efficacy.

• Tumor volumes in cc are calculated for TDx, TPreRx and TPostRx.

• Extrapolates back to the time of tumor initiation thus calculating how long it took for the tumor to reach the initial tumor diameter.

• Calculates approximate time to death in the absence of therapy, assuming constant tumor growth rate.

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