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Major Radiation Oncology Advances 2012 in China
1Huiming Yu, *Guangying Zhu. 1Department of Radiation Oncology, Chaoyang Hospital, Capital Medical University. *correspondent author, Department of Radiation Oncology, Cancer Hospital, Peking University, Beijing, 100142.
AbstrAct
With the improvement of the accuracy in radiation therapy, radiotherapy is playing a more and more important role in the treatment of tumors. According to the WHO statistics, almost half of the cure of tumor patients was attributed to radiation therapy. In this article, we independently review the advances in clinical radiation oncology research which published by Chinese researchers. The major marked advances of radiation oncology that have the potential to lead to a reduction in mortality from cancers will be discussed.
INtrODUctION
radiotherapy plays an important role in the treatment of cancers. chinese researchers have made many technological advances in the treatment of cancers with radiation therapy. In the past year,
new radiotherapy advances, such as individualized treatment, concurrent chemoradiotherapy, target area sketch standard and therapeutic dose, have been introduced. technological gains in radiotherapy have been used to create more complex and conformal treatment plans, deliver higher target doses, use tighter margins to irradiate smaller treatment volumes and reduce toxicities to normal tissues. the large number of advances affirms that clinical cancer research yields remarkable improvements in survival and quality of life for patients with cancer. Many studies which were highlighted this year capitalized on the use of targeted drugs with radiotherapy that share the same genetic alteration.
ADVANcEs IN HEAD
AND NEcK cANcEr
(HNc)
radiation oncology is no longer one-size-fits-all medicine. Growing scientific understanding of the biology of cancer is enabling researchers to develop highly targeted treatment approaches based on the biologic
Key words: Head and neck cancer; Lung cancer; Upper gastrointestinal carcinoma;
Lymphoma; Breast cancer
character of the individual or the tumor. A clinical trial found that a new imaging agent could predict the curative effect of radiotherapy for head and neck cancer.1 Using
18F labelled fluoroquinazoline as PEt/ct imaging agent, they found that the results in the uptake of imaging agent in 27 patients with locally advanced head and neck cancer before or during radiotherapy and chemotherapy indicated there were significant differences in the process of hypoxia and reoxygenation between primary tumors and metastatic lymph nodes. the metastatic lymph nodes with less reoxygenation indicated a poor prognosis including lower overall survival rate. King et al2 reported
that early intratreatment diffusion-weighted imaging has the potential to allow prediction of treatment response at the primary site in patients with primary HNc. A second study found that gross primary tumor volume is an independent prognostic indicator for treatment outcome after intensity modulated radiation therapy (IMrt).3
A control study involving 168 patients with HNc found that patients treated with preoperative radiotherapy with concurrent cisplatin 30 mg/m2 weekly chemotherapy, compared with preoperative radiotherapy alone, could not extend overall survival time, but it could prolong disease-free survival time in patients with locally advanced hypopharyngeal carcinoma and laryngeal cancer.4 In an
open-label phase 3 multicentre randomised controlled trial, the researchers found that adjuvant cisplatin and fluorouracil chemotherapy concurrent with radiotherapy could not significantly improve failure-free survival rate in locally advanced nasopharyngeal carcinoma (NPc).5 similar results were reported by chen et al6 in
a phase III randomized trial. However, some researchers reported contrary results. they found that cisplatin-based chemotherapy plus radiotherapy in patients with NPc increased the risk of treatment-related death and severe acute toxicity, compared with radiotherapy alone.7 A
prospective, randomized study comparing outcomes and toxicities of IMrt with conventional two-dimensional radiotherapy for the treatment of NPc found that IMrt provides improved local-recurrence free survival with a lower incidence of toxicities, especially in late-stage NPc patients.8 Another study found that IMrt re-planning
improves the quality of life as well as local regional control in patients with NPc. Future researches are needed to determine the criteria for replanning for NPc patients undergoing IMrt.9 Data from the randomized phase III
trial showed that docetaxel, cisplatin, and fluorouracil induction chemotherapy improve survival compared with up-front surgery in patients with resectable stage III or IVA oral squamous cell carcinoma. Among patients in the induction chemotherapy arm with a clinical response
or favorable pathologic response had superior Os and locoregional and distant control.10
ADVANcEs IN LUNG cANcEr
Lung cancer remains the leading cause of cancer death in china. People with early stages of the disease rarely have symptoms. As a result, lung cancer is often diagnosed at an advanced stage, when it is difficult to cure.
New research indicates that the epidermal growth factor receptor (EGFr) may eventually prove for predicting the curative effects of concurrent radiotherapy and chemotherapy for non-small cell lung cancer (NscLc). One study found that patients with mutations in the EGFr gene were more sensitive to radiotherapy combined with chemotherapy and had a longer survival period.11 Postoperative chemoradiotherapy can improve
local control rate and reduce or prevent distant metastasis after carefully evaluation of each patient’s age, lung function, basic physical condition scoring and complications to choose a therapeutic schedule that is suitable for the patient.12 For others, such as
targeted treatment with gefitinib, study is beginning. researchers found that gefitinib combined with stereotactic radiosurgery in previously treated patients with advanced NscLc could improve local control and disease-related symptoms, and even increase the progression-free survival and Os.13
As for limited-stage small cell lung cancer (scLc), researchers have proved that radiotherapy according to tumor volumes after two cycles of EP induction chemotherapy could get the similar local control rates and survival rates, reduced side effects than that due to the tumor sizes before induction chemotherapy.14 In a
control study which evaluated the effect of chemotherapy and radiotherapy integration on survival of elderly patients with limited-stage scLc, researchers found that concurrent chemoradiotherapy increased the survival rate and a positive response relationship was observed between dose and survival.15
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ADVANcEs IN UPPEr
GAstrOINtEstINAL cArcINOMA
results from a randomized control design study established involved field radiotherapy as a new standard of care for patients with esophageal squamous carcinoma. researchers found that involved field radiotherapy gets the similar results including survival rate, local control rate and disease-free survival rate in both involved field group and extended field group.17 As for the fractional doses,
researchers reported that moderately hypofractionated radiation reduces the rate of local/regional failure by 20.3% and improves the local control rates by 15.5% than those treated with conventional fractionated radiation.18
compared with the conventional fraction radiotherapy, late course accelerated hyperfraction can improve the local control and survival rates.19 In a randomized,
controlled, multicenter study, researchers have proved that postoperative IMrt plus chemotherapy improved the median duration of recurrence-free survival, but did not significantly improve Os among patients with D2 lymph node dissection in gastric cancer.20
New research indicates that the EGFr inhibitors such as cetuximab may be useful when combined with chemoradiation. In a control study, researchers found that adding cetuximab to definitive concurrent chemoradiation esophageal carcinoma increased clinical complete response by 7.5% in patients with EGFr-expressing tumor than those with negative EGFr expression.21 How to define the gross tumor
volume exactly is the first step to improve the effect of radiotherapy. some researchers found that 4D 18F-FDG PEt/ct is an effective tool to define the target of GtV in radiotherapy.22 Other researchers have found that
postradiation a decreased percentage of tumor FDG uptake was positively correlated with survival time for patients with esophageal cancer. Patients who benefited from radiation were those with a decrease of 30% to 60% in tumor FDG uptake after the completion of radiation.23
ADVANcEs IN LYMPHOMA
Lymphoma is one of common malignant tumors. One research summarized and analyzed the magnetic resonance imaging of 46 initially treated patients with stage I/II NK/t cell lymphoma, with nasopharyngeal local invasion or regional diffusion cell. the study indicated that the determination of individual dose of target volume should refer to magnetic resonance imaging.24 A definitive
study found that combining IMrt with
doxorubicin-based chemotherapy provides favorable outcomes in primary mediastinal large b-cell lymphoma patients with a large target volume and high-risk features.25
radiotherapy combined with chemotherapy improves survival of patients with stage IE/IIE extranodal NK/t-cell lymphoma. A study found that patients with stage IE/IIE extranodal NK/t-cell lymphoma who received first-line combination of gemcitabine, oxaliplatin, and L-asparaginase followed by involved-field radiation therapy can get an effective and feasible treatment results. the overall response rate was 96.3%, and no patients developed disease progression during therapy.26
regional radiotherapy at a total dose of 50 Gy appears to be the standard dose for NK/t lymphoma. While other researchers proved that high-dose and extended involved-field IMrt for patients with early-stage nasal NK/t-cell lymphoma showed favorable locoregional control, overall survival, and progression-free survival, with mild toxicity.27
As for early-stage Hodgkin’s lymphoma with mediastinal involvement, one clinical study proved that involved-field IMrt can give excellent dose coverage and a favorable prognosis.28 Physicians have proved that radical
radiotherapy given at a consistent dose, delivered in 25 installments (fractions), 5 days a week over a period of 5 weeks could significantly expand local control rate29
researchers found that the 3-year overall survival and progression-free survival rates were improved by 26.6% and 17.9% among patients with early stage peripheral t-cell lymphoma through a combination of chemotherapy and radiation therapy compared with chemotherapy alone.30
ADVANcEs IN brEAst cANcEr
breast cancer is one of the concerned tumors. A retrospective study proved that postoperative radiotherapy could enhance the operation curative effects in young patients with breast cancer.31 Another study showed the
same result and further proved that synchronous dosage for treatment patients with stage I-lll breast cancer after breast-conserving surgery was feasible.32 In order to prove
the value of postmastectomy radiation therapy for breast cancer patients with t1-2 tumor and one to three positive nodes, Huang et al33 reported that postmastectomy
radiation therapy is highly recommended for breast cancer patients with t1-2 and one to three positive nodes, especially for high-risk subgroups with a positive nodal ratio of ≥25% and positive lymphovascular invasion, not only for reducing loco-regional recurrence but also for improving disease-free survival.
cONcLUsION
New therapeutic strategies are aimed at not only increasing the efficacy of therapy, but also ensuring similar or lessened toxicity. All chinese professionals for radiation oncology are working actively, and trying hard to make tumor radiotherapy to the world. the major annual advances in this introduction were just a side of performance achieved by china tumor researchers. We hope that more of the public could understand radiotherapy, and fully realize the accuracy, controllability and noninvasive of radiotherapy, and its fast, everlasting and reliable therapeutic effect, and use reasonably radiotherapy to remove sickness from their relatives and friends.
rEFErENcEs
1. Hu Man, Yu Jinming, et al. 2012 AstrO, Abstract No.377 2. King AD, chow KK, Yu KH, Mo FK, Yeung DK, Yuan J, bhatia
Ks, Vlantis Ac, Ahuja At. Head and Neck squamous cell carcinoma: Diagnostic Performance of Diffusion-weighted Mr Imaging for the Prediction of treatment response. radiology 2012 Nov 14. [Epub ahead of print]
3. Guo r, sun Y, Yu XL, Yin WJ, Li WF, chen YY, Mao YP, Liu LZ, Li L, Lin AH, Ma J. Is primary tumor volume still a prognostic factor in intensity modulated radiation therapy for nasopharyngeal carcinoma? radiother Oncol 2012;104(3): 294-299
4. Yi Junlin, Gao Li, et al. 2011 AstrO, Abstract No.155 5. chen L, Hu cs, chen XZ, Hu GQ, cheng Zb, sun Y, Li WX,
chen YY, Xie FY, Liang sb, chen Y, Xu tt, Li b, Long GX, Wang sY, Zheng bM, Guo Y, sun Y, Mao YP, tang LL, chen YM, Liu MZ, Ma J. concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma: a phase 3 multicentre randomised controlled trial. Lancet Oncol 2012;13(2):163-171
6. chen QY, Wen YF, Guo L, Liu H, Huang PY, Mo HY, Li NW, Xiang YQ, Luo DH, Qiu F, sun r, Deng MQ, chen MY, Hua YJ, Guo X, cao KJ, Hong MH, Qian cN, Mai HQ. concurrent chemoradiotherapy vs radiotherapy alone in stage II nasopharyngeal carcinoma: phase III randomized trial.J Natl cancer Inst 2011;103(23):1761-1770
7. Zhang AM, Fan Y, Wang XX, Xie Qc, sun JG, chen Zt, Zhu b. Increased treatment-related mortality with additional cisplatin-based chemotherapy in patients with nasopharyngeal carcinoma treated with standard radiotherapy. radiother Oncol 2012;104(3):279-285
8. Peng G, Wang t, Yang KY, Zhang s, Zhang t, Li Q, Han J, Wu G.A prospective, randomized study comparing outcomes and toxicities of intensity-modulated radiotherapy vs. conventional two-dimensional radiotherapy for the treatment of nasopharyngeal carcinoma .radiother Oncol 2012;104(3):286-293
9. Yang H, Hu W, Wang W, chen P, Ding W, Luo W. replanning during intensity modulated radiation therapy improved quality of life in patients with nasopharyngeal carcinoma. Int J radiat Oncol biol Phys 2013;85(1):e47-54.
10. Zhong LP, Zhang cP, ren GX, Guo W, William WN Jr, sun J, Zhu HG, tu WY, Li J, cai YL, Wang LZ, Fan XD, Wang ZH, Hu
YJ, Ji t, Yang WJ, Ye WM, Li J, He Y, Wang YA,Xu LQ, Wang bs, Kies Ms, Lee JJ, Myers JN, Zhang ZY. randomized Phase III trial of Induction chemotherapy With Docetaxel, cisplatin,and Fluorouracil Followed by surgery Versus Up-Front surgery in Locally Advanced resectable Oral squamous cell carcinoma. J clin Oncol 2012 Nov 5. [Epub ahead of print].
11. Zhu Guangying, et al. 2011 AstrO, Abstract No.268
12. chen s, cheng YL, Li st, Ni YJ, Gu b. Effect analysis of chemoradiotherapy after operation in patients with stage III A non-small cell lung cancer. Asian Pac J trop Med 2012;5(10):823-827.
13. Wang Z, Zhu XX, Wu XH, Li b, shen tZ, Kong Qt, Li J, Liu Zb, Jiang Wr, Wang Y,Hou b. Gefitinib combined With stereotactic radiosurgery in Previously treated Patients With Advanced Non-small cell Lung cancer. Am J clin Oncol 2012 Dec 1. [Epub ahead of print]
14. Hu Xiao, chen Ming, et al. 2011 WcLc
15. su J, Zhu s, Liu Z, Li J, shen W, Li r. A study of Elderly Patients With Limited-stage small-cell Lung cancer After combined chemoradiotherapy. Am J ther 2012 sep 12. [Epub ahead of print]
16. Zhang Hongqing, Yuan Zhiyong, et al. 2012 AstrO, Abstract No.252
17. Qiao Xueying, Li ren, et al. 2012 AstrO, Abstract No.102 18. Ma Jb, Wei L, chen Ec, Qin G, song YP, chen XM, Hao cG.
Moderately hypofractionated conformal radiation treatment of thoracic esophageal carcinoma. Asian Pac J cancer Prev 2012;13(8):4163-4167
19. Wang JH, Lu XJ, Zhou J, Wang F. A randomized controlled trial of conventional fraction and late course accelerated hyperfraction three-dimensional conformal radiotherapy for esophageal cancer. cell biochem biophys 2012;62(1):107-112
20. Zhu WG, Xua DF, Pu J, Zong cD, Li t, tao GZ, Ji FZ, Zhou XL, Han JH, Wang cs, Yu cH, Yi JG, su XL, Ding JX.. A randomized, controlled, multicenter study comparing intensity-modulated radiotherapy plus concurrent chemotherapy with chemotherapy alone in gastric cancer patients with D2 resection. radiother Oncol 2012;104(3):361-366.
21. chen Y, Wu X, bu s, He c, Wang W, Liu J, Guo W, tan b, Wang Y, Wang J. Promising outcomes of definitive chemoradiation and cetuximab for patients with esophageal squamous cell carcinoma. cancer sci 2012;103(11):1979-1984
22. Wang Yc, Hsieh tc, Yu cY, Yen KY, chen sW, Yang sN, chien cr, Hsu sM, Pan t, Kao cH, Liang JA. the clinical application of 4D 18F-FDG PEt/ct on gross tumor volume delineation for radiotherapy planning in esophageal squamous cell cancer. J radiat res 2012;53(4):594-600
23. Ma Jb, song YP, Yu JM, Zhou W, cheng Ec, Zhang XQ. Linear correlation between patient survival and decreased percentage of tumor [(18)F]fluorodeoxyglucose uptake for late-course accelerated hyperfractionated radiotherapy for esophageal cancer. Int J radiat Oncol biol Phys 2012;82(4): 1535-1540.
24. Wu runye, Li Yexiong, et al. 2012 AstrO, Abstract No.180 25. Xu LM, Li YX, Fang H, Jin J, Wang WH, Wang sL, Liu YP, song
YW, Liu QF, chen b, Qi sN, ren H, Dai Jr. Dosimetric Evaluation and treatment Outcome of Intensity Modulated radiation therapy After Doxorubicin-based chemotherapy for Primary Mediastinal Large b-cell Lymphoma. Int J radiat Oncol biol Phys 2012;s0360-3016(12):03737-6
26. Wang L, Wang ZH, chen XQ, Li YJ, Wang KF, Xia YF, Xia ZJ. First-line combination of gemcitabine, oxaliplatin, and L-asparaginase (GELOX)followed by involved-field radiation therapy for patients with stage IE/IIE extranodal natural killer/t-cell lymphoma. cancer 2013;119(2):348-355.
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ZH. Dosimetric and clinical outcomes of involved-field intensity-modulated radiotherapy after chemotherapy for early-stage Hodgkin’s lymphoma with mediastinal involvement. Int J radiat Oncol biol Phys 2012;84(1):210-216
28. Wang H, Li YX, Wang WH, Jin J, Dai Jr, Wang sL, Liu YP, song YW, Wang ZY, Liu QF, Fang H, Qi sN, Liu XF, Yu ZH.Mild toxicity and favorable prognosis of high-dose and extended involved-field intensity-modulated radiotherapy for patients with early-stage nasal NK/t-cell lymphoma. Int J radiat Oncol biol Phys. 2012;82(3):1115-1121
29. shen Qianwen. 2011 AstrO, Abstract No.41
30. Zhang XM, Li YX, Wang WH, Jin J, Wang sL, Liu YP, song YW,
Fang H, ren H, Zhou. survival Advantage With the Addition of radiation therapy to chemotherapy in Early stage Peripheral t-cell Lymphoma, Not Otherwise specified. Int J radiat Oncol biol Phys. 2012;s0360-3016(12):03401-03403
31. tang Lichen, chen Jiayi, et al. 2011 AstrO, Abstract No.66 32. Peng ran, Wang shulian, et al. 2012 AstrO, Abstract No.209 33. Huang cJ, Hou MF, chuang HY, Lian sL, Huang MY, chen FM,
Fu OY, Lin sF. comparison of clinical outcome of breast cancer patients with t1-2 tumor and one to three positive nodes with or without postmastectomy radiation therapy.Jpn J clin Oncol 2012;42(8):711-720
