Solid tumor models for the assessment of different treatment modalities: systematics of response to radiotherapy and chemotherapy.

Abstract

The change of tumor volumes (efficiency) with local tumor radiation doses from 375 R to 3750 R and 5-fluorouracil The multiplicity of genetic, biochemical, metabolic, and morphological differences found in over 40 different lines of Morris hepatomas provides an extremely broad spectrum of solid tumors (8, 9). The ability to utilize specific tumor lines to answer specific questions from this large and diverse group of solid tumors has many advantages for studies on the effects of different forms of treatment in solid tumors.Changes in tumor growth curves are one of the basic and sometimes the only means of evaluation of tumors as well as their response to treatment (10-15). The subject of this report is a continuing search for more critical analytical methods for evaluating tumor growth. A computer program is described and its application to both chemotherapy and radiotherapy is discussed. MATERIALS AND METHODSFemale ACI rats were inoculated subcutaneously in the back with 3924A hepatoma cells by Dr. Harold Morris in Washington, D.C., and shipped to this laboratory. The rats were maintained under standard laboratory conditions including commercial laboratory rat chow (Charles River Laboratories, Wilmington, Mass.) supplied ad libitum, and a 12 hr lighting schedule, the dark period beginning at 8:00 p.m.Tumor volumes (mm3) were calculated from measurements of length, width, and height. The volume is then obtained from the empirical formula 'k L X W X H (13). The tumors were measured and the rats were weighed daily before radiation and for 6 days afterward. The measurements and rat weights were taken three times weekly until the rats were sacrificed.Tumors were x-irradiated locally with 250 kVp at the rate of 800 R/min with a 0.5 mm Cu and 1.0 mm Al filter by a 2 cm cone. The rest of the body was shielded and received about 0.5% of the dose delivered to the irradiated tumor.The rats in the radiation studies were divided into nine groups of 16 rats each. One group of 16 rats acted as control and the other six groups were given 375 R, 750 R, 1500 R, 2250 R, 3000 R, and 3750 R of radiation locally to the tumor (1 R = 2.6 X 10-4 coulomb/kg). The mean tumor size of each group at the time of irradiation was approximately 250 + 50 mm3. Two additional groups of 16 rats each were given 1500 R of irradiation when the mean tumor size was 400 mm3 and 800 mm3.The rats in the 5-fluorouracil studies were divided into six groups of 12 rats each. One

Volumetric tumor growth in advanced non‐small cell lung cancer patients with EGFR mutations during EGFR‐tyrosine kinase inhibitor therapy

“…Characterizing tumor growth rates has been a challenging topic for cancer researchers. Since the 1970s, various studies have attempted to characterize tumor growth dynamics of untreated and treated tumors to better understand solid tumor biology and improve therapeutic management . Recently, the concept of tumor growth rate during anticancer treatment was studied in a trial of patients with solid tumors to define the optimal trial endpoint .…”

“…Since the 1970s, various studies have attempted to characterize tumor growth dynamics of untreated and treated tumors to better understand solid tumor biology and improve therapeutic management. [37][38][39][40][41][42] Recently, the concept of tumor growth rate during anticancer treatment was studied in a trial of patients with solid tumors to define the optimal trial endpoint. 49,50 Gomez-Roca et al studied 76 patients with solid tumors who were treated on phase 1 trials, including patients with NSCLC (n 5 21), and used tumor volume estimated from tumor size.…”

“…Although the growth of most untreated tumors has been well described by the Gompertzian equation, the growth of treated tumors presents another investigational challenge . In the late 1970s, Looney et al quantitatively evaluated tumor growth curves in rat hepatoma during radiotherapy and chemotherapy, attempting to more precisely evaluate therapeutic effects, improve therapeutic scheduling, and better understand tumor biology . Those studies, performed more than 3 decades ago, although technologically different, share similar concepts with the current study, in that they focused on the tumor growth rate during therapy to improve response assessment and therapeutic decisions.…”

Automated image analysis tool for tumor volume growth rate to guide precision cancer therapy: EGFR-mutant non-small-cell lung cancer as a paradigm

“…The module has a function to automatically calculate the tumor volume growth rate over time from the nadir. The calculation of tumor growth rate is performed using the natural logarithm (log e V) of the tumor volume originally measured in mm 3 , as described in prior studies 30,37–40 . For a given patient, the most recent scan can be studied to determine if rapid tumor growth has taken place as defined in the publication on the tumor growth rate in the EGFR-mutant patients, in order to establish “fast” or “slow” tumor growth.…”

Response kinetics of host and experimental solid tumour after adriamycin

“…THE kinetics of recovery for tumour and host organs after treatment with 5-fluorouracil (FU) have recently been determined for the experimental solid-tumour system, hepatoma 3924A (Kovacs et al, 1975;Hopkins et al, 1976;Looney et al, 1976) and these data have been used in the design of an effective chemotherapyradiotherapy combination for this tumour . The present report summarizes data obtained for hepatoma 3924A and its host the ACI rat after treatment with adriamycin (Adr), a relatively new chemotherapeutic agent which is effective against a wide range of human neoplasms (Carter, 1975).…”