Devita, Hellman, and Rosenberg's Cancer

LWBK1006-07 LWW-Govindan-Review November 22, 2011 13:54

92 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

small number of fractions. A meta-analysis showed that hyperbaric oxy-

gen improves the local control of solid tumors by approximately 10%.

Unfortunately, a randomized trial published recently showed that epoetin

b did not improve cancer control or survival in patients with head and

neck cancer.

Answer 7.10. The answer is B.

Hyperfractionation refers to a radiotherapy schedule that uses multi-

ple daily treatments more than 6 hours apart with reduced fraction size

and increased number of fractions. A randomized trial performed by the

European Organization for Research and Treatment of Cancer (EORTC)

showed that a hyperfractionated regimen was significantly better than

standard fractionation in improving local control. Accelerated fractiona-

tion reduces the overall treatment time. It delivers the same dose with the

same fraction size but in a shorter overall treatment time. An RTOG 9003

randomized trial showed that standard fractionation treatment was infe-

rior to hyperfractionation and accelerated fractionation with concomi-

tant boost used for advanced head and neck squamous cell carcinomas.

CHART, as developed at Mt. Vernon Hospital in the United Kingdom,

gave a 54 Gy total dose, which is significantly lower than the standard

fractionated treatment dose for lung cancer.

Answer 7.11. The answer is A.

The two proposed reasons for combining chemotherapy with radiation

therapy includes radiosensitization and spatial additivity. The former con-

cept theoretically may yield synergistic effective which is greater than sim-

ply adding the two together. Gemcitabine is a potent radiosensitizer due

to the induction of dATP depletion and redistribution of the cells into

the early S phase. Although full dose gemcitabine can be safely combined

with radiation therapy for the treatment of locally advanced pancreatic

carcinoma in cases without involved lymph nodes, including the regional

lymph nodes in the radiation field can be extremely toxic. Cisplatin, 5-

fluorouracil, and paclitaxel are also radiosensitizers. Paclitaxel in combi-

nation with radiation (with cis- or carboplatin) has demonstrated clinical

benefit in locally advanced lung therapy. Mechanism of cisplatin radiosen-

sitization is related to its ability to cause inter- and intrastrand DNA cross

links. Two possible explanation are that cisplatin inhibits repair of radia-

tion induced DNA double-strand breaks, or increases the number of lethal

radiation-induced double-strand breaks.

Answer 7.12. The answer is C.

Localized heat treatment can be delivered with microwaves, ultrasound,

or radiofrequency sources of energy. The temperature 42.5◦C appears

to be critical, with small increments above this temperature leading to

a steep increase in lethality. The lethality of hyperthermia is thought to

be in part from denaturation of proteins. Unlike radiation-induced kill,

lethality from heat is most pronounced when cells are in the radio-resistant

S phase. When hyperthermia and radiation are combined in vitro, the net