Tumor volume

Figure 3.1 Time course of implanted tumor volume for one experimental subject (Control) and associated fitted model curves (solid line, exponential model dashed line, nonparametric kernel estimate).

One further question that has a substantial impact on the application of modeling techniques to biomedical problems is the choice of the design. Suppose that in our Gompertz tumor growth example we wanted to decide, given the results of some pilot experiments, when it is most useful to observe the tumor volume. In other words, we wish to choose the time points at which we obtain tumor volume observations in order to maximize the precision of the resulting parameter estimates. 

FIGURE 85-2. The Gompertzian growth curve demonstrating symptoms and treatments versus tumor volume. (From Buick RN. Cellular basis of chemotherapy. In Dorr RT, Von Hoff DD, (eds.) Cancer Chemotherapy Handbook. 2nd ed. New York Elsevier 1994 3-14.)... 

Large tumor volume in a woman with small breasts (better cosmetic results often can be obtained with mastectomy and reconstruction)... 

Patients at high risk of recurrence [stage T3b, a Gleason score ranging from 8 to 10, or a PSA value greater than 20 ng/mL (20 mcg/L) ] should be treated with androgen ablation for 2 to 3 years combined with radiation therapy26 (see Table 89-5). Selected individuals with a low tumor volume may receive a radical prostatectomy or radiation therapy.29,30... 

Prostatic tumor volume contributes to the levels of serum PSA as well as pathological staging, with higher PSA concentrations associated with advanced staging. In the majority of men, PSA concentrations at the time of surgery were found to be <4 ng/ml (organ confined). Half of those with PSA concentrations > 10 ng/ml had capsular penetration, whereas those with PSA values >50 ng/ml showed positive pelvic lymph nodes. 

ABT-888 (22) shows limited activity as monotherapy however, it strongly potentiates the activity of multiple DNA-damaging agents in preclinical models [39]. ABT-888 potentiated TMZ in a glioma model in a dose-dependent manner, with maximal efficacy achieved at 50 mg/ kg, which reduced tumor volume by 63%, 44% better than TMZ alone. In the MX-1 breast xenograft model, ABT-888, at 5 mg/ kg/ day in combination with cisplatin, caused sustained regressions in 8/9 mice compared to 3/9 for cisplatin monotherapy. 

Raloxifene, a more complete uterine antagonist than tamoxifen or clomiphene, significantly reduces leiomyoma size in post-menopausal women [31], yet it is less efficacious at reducing tumor volume in pre-menopausal women [32], This result has been attributed to the poor pharmacokinetic properties of this compound in which extensive conjugative metabolism of the phenol(s) limits the circulating levels of the parent drug. In addition, clinical outcomes in premenopausal women treated with raloxifene suggest that this compound, like tamoxifen and clomiphene, can affect the ovaries via the HPO axis [33]. These data, taken collectively, indicate that current SERMs lack the efficacy, pharmacokinetic, and ovarian safety properties needed to treat leiomyoma in ovulatory women. 

Humphrey and Seal9 (U.S.A.) reported in 1959 detailed experiments on the ECT of sarcoma-180 tumors in nearly 500 mice. In a typical experiment, 18 test animals and 18 control animals were used the ECT was done with 3 ma current, at 6 V for 3 hours a day, for 24 days. They observed that after such a lengthy treatment, the mean volume of test tumors was about 15% of the mean tumor volume of the control group seven mice showed complete tumor regression as a result of ECT. Total regression means that the tumor has decreased progressively in volume, hardened, dropped off, leaving a new skin surface at the former tumor site. 

In the work of Cabrales and coworkers73 (Cuba), sixty male BALBC mice were used and Ehrlich tumors were implanted in them. When the tumor volumes reached 850 mm,3 four platinum electrodes were inserted into each tumor ECT was carried out at 4 mA for 21 minutes, total charge thus passed through each tumor was around 5 coulombs. Tumor volume decrease and necrosis percentage increase were significant in mice treated with ECT, in comparison with the control group without ECT. 

It is clear that in these studies on the ECT of solid tumors in mice, an appreciable reduction in the tumor volume or its complete necrosis is generally observed. 

Fig. 2.3 Therapeutic effect of dEpoB and padi- on days 6, 8,10,12 and 14. o, control with taxel (Taxol ) in nude mice bearing CCRF- vehicle only co, paclitaxel 20 mg/kg and X, CEM/paclitaxel xenografts (57-fold resistant to dEpoB 30 mg/kg. The average tumor volume of paclitaxel) following Q2D x 5, i.v. 6 h infusion. the control group on days 12,14,16,18, and 24...

Figure 9 Tumor growth inhibition study in nude mice implanted with human colon cancer cells. The mean tumor volume from each group was blotted against the number of days. Each group involved eight animals. For clarity, error bars were omitted. Note that after 1.5 weeks the dose, normalized for paclitaxel, was tripled in all treatment groups. Source. From Ref. 43...

Phase 1 dose-escalating and PK studies of Vatalanib were performed on a wide spectrum of tumors including colorectal, RCC, NSCLC, AML, ghoblas-toma, and prostate cancer. Dose ranged up to 2000 mg once daily or 1000 mg twice daily by oral administration. In most studies, results in patients with advanced solid tumors indicated that treatment was well tolerated with no drug-related serious adverse events. Tumor volume reduction was observed in some patients. The MTD was not reached with doses up to 1500 mg/day. The optimal dose was determined as 1250 mg/day. Measurable responses of tumor volume reduction were observed in 19% and 4% of the patients with RCC and ghoblastoma, respectively. Over 50% of patients achieved stable disease [282]. 

Fig. 1. This example of a cumulative dose volume histogram (DVH) exemplifies the manner in which three dimensional treatment planning allows the radiation oncologist to ensure that the tumor receives the planned dose while limiting the dose of radiation received by the normal structures. In this example 100% of the gross tumor volume (GTV) receives 70 Gy whereas the dose received by any length of the spinal cord is less than 45 Gy.

Socinski et al. have reported on their phase I/II experience with dose-escalated thoracic radiation in the setting of a combined modality approach to locally advanced NSCLC (55,64). Two cycles of carboplatin and paclitaxel (AUC 6 and 225 mg/m2/3h q21d) were followed on d 43 by weekly carboplatin and paclitaxel (AUC 2 and 45 mg/ m2/3h x 6) and thoracic radiotherapy (TRT), 50 Gy was delivered to the prechemotherapy tumor volume and areas of suspected microscopic spread in the mediastinum with a 1.0-2.0 cm margin. Boost volumes included the primary tumor volume and all radiographically positive nodes with a 1.0 cm margin. The total dose of radiation was escalated through four cohorts of patients 60,66,70,74 Gy without reaching any of the planned toxicity endpoints. The overall response to the therapy was 50% (3% CR, 47%... 

The standard for radiation port size without chemotherapy for limited-stage SCLC is a relatively large port, which includes the original tumor volume with a 1.5-2 cm free margin (37,38). Included with the tumor are the involved lymph nodes as well as the neighboring uninvolved lymph nodes. A retrospective review of the SECSG trial re-... 

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