Dear Dr Rajawat

It is really difficult case  but with new progress in SBRT , I hope it will help you 

I recommend to read this paper 

Best Wishes

Habib

J Gastrointest Oncol. 2014 Jun; 5(3): 190–197.

doi: 10.3978/j.issn.2078-6891.2014.039

PMCID: PMC4074953

Stereotactic body radiation therapy for liver metastases

Marta Scorsetti,corresponding author Elena Clerici, and Tiziana Comito

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Abstract

Over the years, early diagnosis of metastatic disease has improved and the prevalence of oligometastatic patients is increasing. Liver is a most common site of progression from gastrointestinal, lung and breast cancer and in the setting of oligometastatic patients, surgical resection is associated with increased survival. Approximately 70-90% of liver metastases, however, are unresectable and an effective and safe alternative therapeutic option is necessary for these patients. The role of stereotactic body radiation therapy (SBRT) was investigated in the treatment of oligometastatic patients with promising results, thanks to the ability of this procedure to deliver a conformal high dose of radiation to the target lesion and a minimal dose to surrounding critical tissues. This paper was performed to review the current literature and to provide the practice guidelines on the use of stereotactic body radiotherapy in the treatment of liver metastases. We performed a literature search using Medical Subject Heading terms “SBRT” and “liver metastases”, considering a period of ten years.

Keywords: Liver metastases, stereotactic body radiation therapy (SBRT), oligometastases, stereotactic ablative radiotherapy (SABR)

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Background

Over the years, the concept of metastatic disease has evolved and the therapeutic approach has changed. In 1907 Halsted described his theory on the spread of breast cancer, perhaps the first modern theory on cancer metastasis. He proposed an orderly spatial and temporalprogression from primary site to locoregional lymphatics and ultimately to disseminated disease. Radical locoregional therapy was thought reduce the risk of metastatic disease by removing the source of metastases (1). Subsequently, other researchers, notably Dr. Bernard Fisher, who also studied breast cancer, proposed that metastasis was a systemic phenomenon, and that local therapy could do little to affect a patient’s survival once the cancer had metastasized (2). Since then, the historical concept of metastic disease as an incurable state for which only systemic therapies and palliative interventions are appropriate has been questioned. In the 1990’s Weichselbaum and Hellman formulated a new hypothesis, according to which the metastatic disease is exists as part of a “spectrum” of clinical states. The intermediate state, called “Oligometastatic disease”, represented a condition between the absence of metastases and widespread dissemination (3). Patients with oligometastatic disease might potentially enjoy extended survival or even be cured with aggressive local therapy to their metastatic tumor sites. Recent improvements in diagnostic imaging have allowed the early diagnosis of metastatic disease in a higher number of patients and nowadays the prevalence of patients in the oligometastatic state is increasing (4).

Colorectal cancer (CRC) is one of the tumors that most often presents with solitary or oligometastasic disease, commonly in the liver. It is estimated, indeed, that 30% to 70% of patients with CRC will develop liver metastases and in this subset, hepatic progression is an important cause of morbidity and mortality (5,6). In patients with untreated colorectal liver metastases the overall survival (OS) is about 31% at 1 year, 8% at 2 years, 3% at 3 years, and 1% at 4 years, with a median survival ranging from 6 to 12 months (7). The introduction of modern chemotherapy regimens in the current treatment for colorectal liver metastases has improved the progression free survival rate and to a lesser extent the OS, due tolimited local control (LC) of disease (8-10). Historically, surgical resection of CRC liver metastases improves OS, with 1 and 5-year rates of 90-95% and 30-60%, respectively and with a median OS of 40-53 months (11-14). In 1999, Fong et al. defined the main favorable prognostic factors for oligometastatic CRC patients treated with surgery of liver metastases and included the absence of extrahepatic disease, metachronous presentations with extended disease-free intervals (DFI) >12 months, single metastasis 70), with absentt or stable extrahepatic disease and adequate hepatic volume and function.

Prescription doses, generally ranged from 30 to 60 Gy in 3 fractions, although in one published phase II trial a higher prescription dose of 75 Gy in 3 fractions was delivered (41). In two prospective studies a single fraction of 14-30 Gy was employed (35,36) and in one phase I trial an individualized radiation doses ranging from 27.7 to 60 Gy in 6 fractions was delivered (35).

Most studies showed a low toxicity profile with a ≥ G3 toxicity rate of 1-10% and the incidence of RILD less than 1%. Lee et al. (35), did not experience RILD in 68 patients treated with 6 fractions and median liver dose of 16.9 Gy (range, 3-22 Gy). In a phase I/II study by Rusthoven et al. (37) on 47 patients and in a phase II trial by Scorsetti et al. (41) on 61 patients, no RILD was observed using a dose constraint allowing no more than 700 mL of uninvolved liver to receive 15 Gy or greater in 3 fractions. The most common G2 toxicities included a transient hepatic transaminase increase within 3 months of SBRT (39,41) and gastrointestinal, soft-tissue and bone complications, related to lesions close to the duodenum, bowel, skin and ribs. Duodenal ulceration and intestinal perforation were observed in 3 patients with maximum doses greater than 30 Gy in 3 fractions to the duodenum and bowel (40). One case of Grade 3 soft-tissue toxicity was observed for dose of 48 Gy in 3 fractions to a subcutaneous tissue (37). In 2 patients, nontraumatic rib fractures were experienced for maximum doses of 51.8 Gy and 66.2 Gy in 6 fractions to 0.5 cm3 of rib (35). One patient suffered from chronic chest wall pain G3, which resolved within 1 year after SBRT for a prescription dose of 75 Gy in 3 fractions (41).

LC rates varies from 70% to 100% at 1 year and 60% to 90% at 2 years and correlated to lesion size 3 cm compared with smaller metastases, using an ablative prescription dose of 75 Gy in 3 fractions (41).

Two-years OS rate was 30-83%, with a median OS rate ranging from 10 to 34 months. OS correlation with lesion size higher than 3 cm and metachronous presentation for CRC liver metastases was demonstrated by Hoyer et al. (40).

SBRT for liver metastases: practice guideline

Patient selection

Selection criteria for patients with liver metastases candidate to SBRT are controversial and a multidisciplinary tumor board discussion is recommended. Figure 1 shows the patient’s treatment algorithm. According to the current literature, patients who may be candidates for SBRT can be separated into three categories: suitable, cautionary and unsuitable patients. Table 2 shows the characteristics for all groups.

Figure 1

Figure 1

Patient’s treatment algorithm. CT, computed tomography; PET, positron emission tomography; MRI, magnetic resonance imaging.

Table 2

Table 2

Selection criteria for SBRT

The best candidates for SBRT are oligometastatic patients with a good performance status (Eastern Cooperative Oncology Group 0-1 or Karfnosky >70), controlled or absent extra-hepatic disease, number of hepatic lesions ≤3, size lesions ≤3 cm, lesion distance from organs at risk (OARs) >8 mm, good liver function (Childs A) and healthy liver volume >1,000 cc. In patients with 4 liver metastases, diameter ranging from 3 to 6 cm, OARs distance between 5 and 8 mm, moderate liver function (Child B) and healthy liver volume ranging from 700 to 1,000 cc, the use of SBRT must be evaluated with caution. Patients with ≥5 hepatic lesions, diameter greater than 6 cm, OARs distance less than 5 mm, inadequate liver function (Child C) and healthy liver volume 3 cm a higher prescription dose is necessary to obtain similar LC (41) (Table 3).

Table 3

Table 3

Prescription dose in 3 fractions recommended according to lesion diameter

Recommended dose constraints for OARs are listed in Table 4 (37,41). In case of overlap between the PTV and gastrointestinal tract or heart, the priority should be given to OARs (41).

Table 4

Table 4

Recommended OARs dose constraints for liver SBRT in 3 fractions

Response evaluation

Assessment of tumor response can be performed based on European Organization for Research and Treatment of Cancer Response Evaluation Criteria In Solid Tumors (EORTC-RECIST) criteria (45) and MRI can be used during the follow up especially for hepatic lesions poorly detected on CT. The radiographic response after SBRT are typically slow, as demonstrated by Herfath et al. which showed the progressive radiographic response and the characteristic reduction of focal liver reaction after 2-4 months and 11-15 months respectively, in our series (42). If PET-CT is performed before SBRT, it is recommended to employ PET Response Criteria in Solid Tumors (PERCIST) (47), as showed in Table 5. Figure 2 shows the complete metabolic response (CMR) in a single hepatic lesion after SBRT.

Table 5

Table 5

EORTC-RECIST and PERCIST criteria for evaluation of tumor response

Figure 2

Figure 2

Example of complete metabolic response in a single hepatic lesion treated with SBRT. SBRT, stereotactic body radiation therapy.

Thanks for asking the question. Will keep in mind if I come across any such article showing an alternative and better treatment option.

Suggestion from Roman.

in response to your question with nicely written description of a case of metastatic LMS, I suggest that you consider the following two options:

1. Trabectidin (YONDELIS), which has been approved by the FDA for recurrent or metastatic LMS in patients previously treated with doxorubicin.

For scientific article reference see the following:

https://www.ncbi.nlm.nih.gov/pubmed/19652065

2. Ridaforolimus is another option, which allows long term maintenance treatment with oral administration. This is, however, an experimental therapeutic in clinical evaluation and may be difficult to obtain.

http://investor.ariad.com/phoenix.zhtml?c=118422&p=irol-newsArticle&ID=1570938

http://www.futuremedicine.com/doi/abs/10.2217/fon.11.57?journalCode=fon

Best Regards,

Roman

@Roman: Thank you very much for your wonderful suggestions.

@habibollah: Thank you very much for the suggestions. I will definately go through the article and will keep in mind regarding the same. I am sure it will help the patient. If you find any more updates, kindly do let me know. Thanks :-)

@ varshil: Thanks a lot. :-)