NCCN Guidelines® Insights: Biliary Tract Cancers, Version 2.2023.

In 2023, the NCCN Guidelines for Hepatobiliary Cancers were divided into 2 separate guidelines: Hepatocellular Carcinoma and Biliary Tract Cancers. The NCCN Guidelines for Biliary Tract Cancers provide recommendations for the evaluation and comprehensive care of patients with gallbladder cancer, intrahepatic cholangiocarcinoma, and extrahepatic cholangiocarcinoma. The multidisciplinary panel of experts meets at least on an annual basis to review requests from internal and external entities as well as to evaluate new data on current and emerging therapies. These Guidelines Insights focus on some of the recent updates to the NCCN Guidelines for Biliary Tract Cancers as well as the newly published section on principles of molecular testing.

Hepatobiliary Cancers, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.

The NCCN Guidelines for Hepatobiliary Cancers focus on the screening, diagnosis, staging, treatment, and management of hepatocellular carcinoma (HCC), gallbladder cancer, and cancer of the bile ducts (intrahepatic and extrahepatic cholangiocarcinoma). Due to the multiple modalities that can be used to treat the disease and the complications that can arise from comorbid liver dysfunction, a multidisciplinary evaluation is essential for determining an optimal treatment strategy. A multidisciplinary team should include hepatologists, diagnostic radiologists, interventional radiologists, surgeons, medical oncologists, and pathologists with hepatobiliary cancer expertise. In addition to surgery, transplant, and intra-arterial therapies, there have been great advances in the systemic treatment of HCC. Until recently, sorafenib was the only systemic therapy option for patients with advanced HCC. In 2020, the combination of atezolizumab and bevacizumab became the first regimen to show superior survival to sorafenib, gaining it FDA approval as a new frontline standard regimen for unresectable or metastatic HCC. This article discusses the NCCN Guidelines recommendations for HCC.

Guidelines Insights: Hepatobiliary Cancers, Version 2.2019.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and updated recommendations regarding systemic therapy for first-line and subsequent-line treatment of patients with hepatocellular carcinoma.

NCCN Guidelines Insights: Hepatobiliary Cancers, Version 1.2017.

The NCCN Guidelines for Hepatobiliary Cancers provide treatment recommendations for cancers of the liver, gallbladder, and bile ducts. The NCCN Hepatobiliary Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding locoregional therapy for treatment of patients with hepatocellular carcinoma.

Impact of adjuvant chemoradiation on survival in patients with resectable cholangiocarcinoma.

BACKGROUND: The ideal adjuvant therapy for resected cholangiocarcinoma remains controversial. National guidelines stratify recommendations based on margin status, though few studies are currently available for reference. METHODS: Data was abstracted on all patients with definitive resections of cholangiocarcinoma at our institution between 2000 and 2013. Adjuvant chemoradiation consisted of 45 Gy delivered to elective nodal regions and 50.4-54 Gy to the surgical bed with concurrent fluoropyrimidine-based chemotherapy. Subgroup analyses were performed delineated by margin status. RESULTS: Curative resection was performed on 95 patients followed by adjuvant chemoradiation in 23/95 (24%) and observation in 72/95 (76%) with a median follow-up of 21.7 months. For those receiving adjuvant chemoradiation the median overall survival was 30.2 months compared with 26.3 months for those observed (p = 0.0695). In a multivariable model controlling for other prognostic factors, adjuvant chemoradiation was associated with improved disease-free survival (HR 0.50, p = 0.03) and overall survival (HR 0.37, p = 0.004). In multivariable models stratified by margin status, adjuvant chemoradiation was associated with improved overall survival following both margin-negative (HR 0.34, p = 0.035) and margin-positive (HR 0.15, p = 0.003) resections. CONCLUSIONS: Overall survival was improved with adjuvant chemoradiation following either margin-negative or margin-positive resections, which is not currently reflected in national guidelines.

Adjuvant stereotactic body radiotherapy following transarterial chemoembolization in patients with non-resectable hepatocellular carcinoma tumours of ≥ 3 cm.

OBJECTIVES: The optimal locoregional treatment for non-resectable hepatocellular carcinoma (HCC) of ≥ 3 cm in diameter is unclear. Transarterial chemoembolization (TACE) is the initial intervention most commonly performed, but it rarely eradicates HCC. The purpose of this study was to measure survival in HCC patients treated with adjuvant stereotactic body radiotherapy (SBRT) following TACE. METHODS: A retrospective study of patients with HCC of ≥ 3 cm was conducted. Outcomes in patients treated with TACE alone (n = 124) were compared with outcomes in those treated with TACE + SBRT (n = 37). RESULTS: There were no significant baseline differences between the two groups. The pre-TACE mean number of tumours (P = 0.57), largest tumour size (P = 0.09) and total tumour diameter (P = 0.21) did not differ significantly between the groups. Necrosis of the HCC tumour, measured after the first TACE, did not differ between the groups (P = 0.69). Local recurrence was significantly decreased in the TACE + SBRT group (10.8%) in comparison with the TACE-only group (25.8%) (P = 0.04). After censoring for liver transplantation, overall survival was found to be significantly increased in the TACE + SBRT group compared with the TACE-only group (33 months and 20 months, respectively; P = 0.02). CONCLUSIONS: This retrospective study suggests that in patients with HCC tumours of ≥ 3 cm, treatment with TACE + SBRT provides a survival advantage over treatment with only TACE. Confirmation of this observation requires that the concept be tested in a prospective, randomized clinical trial.

Efficacy and toxicity of conventionally fractionated pelvic radiation with a hypofractionated simultaneous versus conventionally fractionated sequential boost for patients with high-risk prostate cancer.

PURPOSE: To determine if high-risk prostate cancer responds differently to hypofractionation. MATERIAL AND METHODS: One hundred and fifty-seven men with NCCN high-risk (T3, PSA > 20, or Gleason ≥ 8) clinically localized prostate cancer treated between 1998 and 2010 met the inclusion criteria for the analysis. Eighty-two were treated with conventional WPRT with a conventionally fractionated sequential boost to the prostate (cRT), with the prostate receiving 75-77 Gy in 1.8-2.0 Gy fractions. Seventy-five were treated with pelvic IMRT with a hypofractionated simultaneous boost to the prostate (hRT), with the prostate receiving 70 Gy in 2.5 Gy fractions. The dose to the pelvic lymph nodes was 45 Gy in the cRT group and 50.4 Gy in the hRT group, both at 1.8 Gy per fraction. Ninety-two percent received neoadjuvant hormonal ablation therapy, typically beginning two months prior to the start of RT. RESULTS: Median follow-up was 6.5 years for men receiving cRT and 3.7 years for those receiving hRT. The actuarial rate of biochemical control at four years was 88% for cRT and 94% for hRT (p = 0.82). The rates of early rectal and urinary grade ≥ 2 toxicities were 35% (29 of 82) and 49% (40 of 82) for the cRT group and 36% (27 of 75) and 44% (33 of 75) for the hRT group. The actuarial rate of late grade ≥ 2 rectal toxicity at four years was 25% for the cRT group and 13% for the hRT group (p = 0.037). The rate of late grade 3 rectal complications was 4% (3 of 82) for patients receiving cRT and 1% (1 of 75) for patients receiving hRT. CONCLUSION: Initial follow-up indicates equivalent biochemical control between regimens. Patients receiving hRT experienced fewer late rectal complications.

Flattening filter-free linac improves treatment delivery efficiency in stereotactic body radiation therapy.

Stereotactic body radiation therapy (SBRT) employs precision target tracking and image-guidance techniques to deliver ablative doses of radiation to localized malignancies; however, treatment with conventional photon beams requires lengthy treatment and immobilization times. The use of flattening filter-free (FFF) beams operating at higher dose rates can shorten beam-on time, and we hypothesize that it will shorten overall treatment delivery time. A total of 111 lung and liver SBRT cases treated at our institution from July 2008 to July 2011 were reviewed and 99 cases with complete data were identified. Treatment delivery times for cases treated with a FFF linac versus a conventional dose rate linac were compared. The frequency and type of intrafraction image guidance was also collected and compared between groups. Three hundred and ninety-one individual SBRT fractions from 99 treatment plans were examined; 36 plans were treated with a FFF linac. In the FFF cohort, the mean (± standard deviation) treatment time (time elapsed from beam-on until treatment end) and patient's immobilization time (time from first alignment image until treatment end) was 11.44 (± 6.3) and 21.08 (± 6.8) minutes compared to 32.94 (± 14.8) and 47.05 (± 17.6) minutes for the conventional cohort (p < 0.01 for all values). Intrafraction-computed tomography (CT) was used more often in the conventional cohort (84% vs. 25%; p < 0.05), but use of orthogonal X-ray imaging remained the same (16% vs. 19%). For lung and liver SBRT, a FFF linac reduces treatment and immobilization time by more than 50% compared to a conventional linac. In addition, treatment with a FFF linac is associated with less physician-ordered image guidance, which contributes to further improvement in treatment delivery efficiency.

Role of chemoradiation in gallbladder cancer-a single institution retrospective analysis.

Background: Gallbladder cancer is one of the highest fatal malignancy. We conducted a retrospective analysis to study the outcomes of gallbladder malignancy in an academic care setting. Methods: Data was collected retrospectively on patients treated at University of Alabama at Birmingham between January 2005 and June 2015 from the electronic medical record using a standardized data collection tool (Redcap). We evaluated for predictors of overall survival (OS) and progression-free survival (PFS). Results: Of the 93 patients in this study, 66.7% were female. Adjuvant chemotherapy (CT) was given to 11% and adjuvant chemoradiation (CRT) to 14%. On multivariate analysis, albumin >3.5 g/dL, uninvolved margins, absence of lymphovascular invasion, and peri-neural invasion were independent predictors of OS and PFS. The overall median survival time was 24.3 months with a 5-year survival rate at 23.7%. Surgery with CRT for the full cohort had a median OS of 54.4 vs. 15.6 months (P=0.0048) compared to surgery CT alone. The OS in stage 3-4 patients with surgery alone vs. surgery & CT was 5.5 vs. 28.7 months, respectively (P=0.0061). The PFS for the same group was 4.6 vs. 17.5 months (P=0.0052). Conclusions: The dismal survival rates of gallbladder cancer made adjuvant therapy (CT or CRT) critically important. Concurrent CRT needs to be evaluated in randomized clinical trials for potential improvement in clinical outcomes compared to currently approved standard of care, adjuvant CT alone.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: 5-Year Toxicity and Biochemical Recurrence Results From a Prospective Trial.

PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly used as a definitive treatment option for patients with prostate adenocarcinoma. The aim of this study was to assess the late toxicity, patient-reported quality of life outcomes, and biochemical recurrence rates after prostate SBRT with simultaneous integrated boost (SIB) targeting lesions defined by magnetic resonance imaging (MRI). METHODS AND MATERIALS: Patients were eligible if they had biopsy-proven low- or intermediate-risk prostate adenocarcinoma, one or more focal lesions on MRI, and an MRI-defined total prostate volume of <120 mL. All patients received SBRT delivered to the entire prostate to a dose of 36.25 Gy in 5 fractions with an SIB to the lesions seen on MRI to 40 Gy in 5 fractions. Late toxicity was defined as any possible treatment-related adverse event occurring after 3 months from the completion of SBRT. Patient-reported quality of life was ascertained using standardized patient surveys. RESULTS: A total of 26 patients were enrolled. Six patients (23.1%) had low-risk disease and 20 patients had intermediate-risk disease (76.9%). Seven patients (26.9%) received androgen deprivation therapy. Median follow-up was 59.5 months. No biochemical failures were observed. Three patients (11.5%) experienced late grade 2 genitourinary (GU) toxicity requiring cystoscopy, and 7 patients (26.9%) had late grade 2 GU toxicity requiring oral medications. Three patients (11.5%) had late grade 2 gastrointestinal toxicity characterized by hematochezia requiring colonoscopy and steroids per rectum. There were no grade 3 or higher toxicity events observed. The patient-reported quality-of-life metrics at the time of last follow-up were not significantly different than the pre-treatment baseline. CONCLUSIONS: The results of this study support that SBRT to the entire prostate to a dose of 36.25 Gy in 5 fractions with focal SIB to 40 Gy in 5 fractions has excellent biochemical control and is not associated with undue late gastrointestinal or GU toxicity or long-term quality of life decrement. Focal dose escalation with an SIB planning approach may be an opportunity to improve biochemical control while limiting dose to nearby organs at risk.

Association of Radiotherapy Duration With Clinical Outcomes in Patients With Esophageal Cancer Treated in NRG Oncology Trials: A Secondary Analysis of NRG Oncology Randomized Clinical Trials.

Importance: For many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes. Objective: To analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT). Design, Setting, and Participants: This study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute-sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023. Exposures: Treatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy. Main Outcomes and Measures: The outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable. Results: The analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07). Conclusions and Relevance: Results of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

Radiation necrosis in the brain: imaging features and differentiation from tumor recurrence.

Radiation necrosis in the brain commonly occurs in three distinct clinical scenarios, namely, radiation therapy for head and neck malignancy or intracranial extraaxial tumor, stereotactic radiation therapy (including radiosurgery) for brain metastasis, and radiation therapy for primary brain tumors. Knowledge of the radiation treatment plan, amount of brain tissue included in the radiation port, type of radiation, location of the primary malignancy, and amount of time elapsed since radiation therapy is extremely important in determining whether the imaging abnormality represents radiation necrosis or recurrent tumor. Conventional magnetic resonance (MR) imaging findings of these two entities overlap considerably, and even at histopathologic analysis, tumor mixed with radiation necrosis is a common finding. Advanced imaging modalities such as diffusion tensor imaging and perfusion MR imaging (with calculation of certain specific parameters such as apparent diffusion coefficient ratios, relative peak height, and percentage of signal recovery), MR spectroscopy, and positron emission tomography can be useful in differentiating between recurrent tumor and radiation necrosis. In everyday practice, the visual assessment of diffusion-weighted and perfusion images may also be helpful by favoring one diagnosis over the other, with restricted diffusion and an elevated relative cerebral blood volume being seen much more frequently in recurrent tumor than in radiation necrosis.

The Clinical Benefit of Adjuvant Therapy in Long-Term Survival of Early-Stage Ampullary Carcinoma: A Single Institutional Experience.

BACKGROUND: The role of adjuvant chemotherapy (CT) or combination chemoradiation (CRT) remains uncertain for ampullary carcinoma (AC). In this analysis, we reviewed our institution's experience with early-stage AC. METHODS: AC patients who had definitive surgical intervention at the University of Alabama, Birmingham, between 2005 and 2015, were identified. Clinicopathologic factors and disease statuses were obtained from chart review. The univariate Cox proportional hazard model was conducted for evaluating the parameters associated with overall survival (OS). Kaplan-Meier method and log-rank method were used to compare the time-to-events. We estimated the survival for the patients who had definitive surgery (pancreaticoduodenectomy (PD) or ampullectomy), and followed them up with assessing the influence of adjuvant treatment (chemoradiotherapy or CT) alone on the survival in the early-stage (stage I/II) AC. RESULTS: A total of 63 patients had definitive surgery. The median OS and progression-free survival (PFS) for all the patients who had definitive surgery were 40.5 months and 28 months, respectively. Adjuvant treatment was administered in 60% of patients with early-stage (stage I/II) AC (CT 36% and CRT 24%), while 22% were on surveillance post surgery. The pathological stage ≥ 2, Lymph node (LN) metastasis, peri-nodal extension (PNE) and peri-pancreatic extension (PPE) were found to be the determinants for poor OS and PFS by univariate analysis. Multiple Cox regression of these variables showed a significant influence of PPE and pathological staging on the OS and PFS, respectively. In the early-stage AC with no high-risk features, adjuvant therapy did not improve the survival over surgery alone (40.5 vs. 51.7 months, P = 0.93). The addition of radiation to CT did not yield improved outcome in early-stage cancers. For CRT and CT, OS was 22.8 versus 65.7 months (P = 0.3975), and PFS was 25.3 versus 65.7 months (P = 0.4699). CONCLUSIONS: In the early-stage AC, adjuvant therapy may not improve the outcome in the short term but may benefit over a long period. It should be considered, especially in patients with adverse risk factors. Radiation therapy may not be useful in managing AC in the adjuvant setting.

THE NOVEL USE OF STEREOTACTIC RADIOTHERAPY FOR REMNANT ADRENAL TISSUE IN NELSON SYNDROME.

OBJECTIVE: Recurrent Cushing disease (CD) is a rare complication that occurs in patients who have undergone bilateral adrenalectomy (BLA). We report a case of recurrent CD in a patient with Nelson syndrome and adrenalectomy due to remnant adrenal tissue, and a novel treatment strategy using stereotactic body radiation therapy (SBRT) to the adrenal glands. METHODS: We report a case of recurrent CD in a woman with Nelson syndrome and adrenalectomy and describe her clinical course and management. We also include a literature review of CD management and adrenal radiation. RESULTS: The patient had persistent pituitary CD despite pituitary surgery and radiosurgery and underwent BLA. She developed recurrent CD due to a remnant adrenal gland post adrenalectomy. She then underwent SBRT to both adrenal beds to treat the remnant adrenal tissue. Her serum cortisol dropped rapidly after adrenal radiation and she experienced minimal side effects. She has been in remission for over 2 years. CONCLUSION: This is the first reported case of recurrent CD in a patient post adrenalectomy that was successfully treated with SBRT to the remnant adrenal tissue.

A case of syringotropic cutaneous T-cell lymphoma treated with local radiotherapy.

Syringotropic cutaneous T-cell lymphoma (SCTCL) is a variant of mycosis fungoides that is characterized by the presence of lymphocytic infiltration of eccrine glandular structures and the absence of the classic features of MF, such as epidermotropism and Pautrier's microabscesses. We report a patient with SCTCL who presented with multiple hypopigmented patches and localized alopecia who was treated with local radiotherapy with excellent local control. In our experience, local electron radiation offers local control in early stage SCTCL, and it may be possible to reserve systemic therapy for more advanced stages of the disease.

Advances in pancreatic cancer biomarkers.

Biomarkers play an essential role in the management of patients with invasive cancers. Pancreatic ductal adenocarcinoma (PDC) associated with poor prognosis due to advanced presentation and limited therapeutic options. This is further complicated by absence of validated screening and predictive biomarkers for early diagnosis and precision treatments respectively. There is emerging data on biomarkers in pancreatic cancer in past two decades. So far, the CA 19-9 remains the only approved biomarker for diagnosis and response assessment but limited by low sensitivity and specificity. In this article, we aim to review current and future biomarkers that has potential serve as critical tools for early diagnostic, predictive and prognostic indications in pancreatic cancer.

Therapeutic options for ampullary carcinomas. A review.

Ampullary Carcinoma arises from a histologically heterogeneous region where three different epithelia converge. Even though Ampullary Carcinoma has a superior prognosis compared to pancreatic and biliary ductal neoplasms, at least half of the patients turn up at an advanced stage that limits the treatment prospects. In addition to surgery for early-stage disease, several studies have shown that chemoradiotherapy confers additional benefits in the management of Ampullary Carcinoma. Analogously, chemotherapy plays a crucial role in treating advanced Ampullary Carcinoma with distant metastasis/recurrences. Although, stage of the disease, lymph node status, and histo-morphology are three critical prognostic variables, recently much attention is being placed on the genetic landscape of Ampullary Carcinoma. In this review, we have discussed various studies describing the role of chemoradiation and chemotherapy in the treatment of early and advanced stage Ampullary Carcinoma. Also, we have summarized the molecular landscape of Ampullary Carcinoma and the novel therapeutic strategies which could possibly target the genetic alterations involving the tumor cells.

Prostate Stereotactic Body Radiation Therapy With a Focal Simultaneous Integrated Boost: Acute Toxicity and Dosimetry Results From a Prospective Trial.

PURPOSE: This study aimed to report the early toxicity results of a prospective clinical trial of prostate stereotactic body radiation therapy (SBRT) to the entire prostate with a simultaneous integrated boost (SIB) to magnetic resonance imaging (MRI)-defined focal lesions. METHODS AND MATERIALS: Eligible patients included men with biopsy-proven prostate stage T1c to T2c adenocarcinoma, a Gleason score ≤7, and prostate-specific antigen values of ≤20 ng/mL, who had at least 1 focal lesion visible on MRI and a total prostate volume no greater than 120 cm3. SBRT consisted of a dose of 36.25 Gy to the entire prostate with an SIB of 40 Gy to the MRI-defined lesions, delivered in 5 fractions. The primary purpose of the study was to confirm the feasibility of treatment planning/delivery and to estimate the rate of urinary retention requiring placement of a Foley catheter within 90 days of treatment. This study was to be considered successful if urinary retention occurred in no more than 15% of cases, with a planned enrollment of at least 25 patients. RESULTS: A total of 26 men were enrolled, and all underwent SBRT as planned. Twenty patients (77%) had intermediate-risk features, and the remainder were low risk. A treatment plan that met the protocol-defined goals for all cases was developed. Two patients (7.7%) developed acute urinary symptoms that required the temporary placement of a Foley catheter. No grade 3+ toxicity events were observed. CONCLUSIONS: Planning and delivery of prostate SBRT with a whole prostate dose of 36.25 Gy and a focal 40 Gy SIB is feasible. Early follow-up suggests that this treatment is not associated with undue morbidity.

Feasibility of Dose Escalating [18F]fluciclovine Positron Emission Tomography Positive Pelvic Lymph Nodes During Moderately Hypofractionated Radiation Therapy for High-Risk Prostate Cancer.

PURPOSE: The aim of this study was to report the treatment planning feasibility of dose escalation to suspicious lymph nodes (LNs) for a series of men who underwent pretreatment [18F]fluciclovine positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS AND MATERIALS: Cases of men with prostate cancer who enrolled in a clinical trial of pretreatment [18F]fluciclovine PET who had suspicious LNs were selected. Pelvic LNs <1 cm were defined as positive based on [18F]fluciclovine-PET if their maximum standardized uptake value (SUVmax) was ≥1.3-fold greater than the reference blood pool SUVmean, and LNs ≥1 cm were defined as positive if the SUV was greater than the reference SUV bone marrow reference. For each case, a radiation treatment plan was generated to deliver 70 Gy to the prostate and proximal seminal vesicles, 60.2 Gy to the PET-positive LNs, and 50.4 Gy to the elective nodal regions, simultaneously in 28 fractions of 2.5 Gy, 2.15 Gy, and 1.8 Gy, respectively. Treatment planning goals were defined a priori. The resulting target volume and organ-at-risk dosimetry were compared with the original treatment plan. RESULTS: Four cases were identified, with between 1 and 5 [18F]fluciclovine PET-positive LNs each. Goals for the prostate and elective nodal target volumes were successfully met in all cases. The goal of covering more than 90% of the positive LN planning target volume by the prescription dose of 60.2 Gy was met in 3 of the 4 cases. This goal was not met in 1 case, but 100% of clinical target volume was covered by 60.2 Gy. The primary organ-at-risk tradeoff was that a small volume (0.5-8.2 cm3) of small bowel would receive ≥54 Gy in each case. CONCLUSIONS: These preliminary results suggest that [18F]fluciclovine PET/MRI directed dose escalation of suspicious pelvic LNs is likely feasible in the setting of definitive radiation therapy. The potential clinical benefit of dose escalating [18F]fluciclovine PET-positive LNs should be investigated in a prospective clinical trial.