Examining guidelines and new evidence in oncology nutrition: a position paper on gaps and opportunities in multimodal approaches to improve patient care.

Malnutrition, muscle loss, and cachexia are prevalent in cancer and remain key challenges in oncology today. These conditions are frequently underrecognized and undertreated and have devastating consequences for patients. Early nutrition screening/assessment and intervention are associated with improved patient outcomes. As a multifaceted disease, cancer requires multimodal care that integrates supportive interventions, specifically nutrition and exercise, to improve nutrient intake, muscle mass, physical functioning, quality of life, and treatment outcomes. An integrated team of healthcare providers that incorporates societies' recommendations into clinical practice can help achieve the best possible outcomes. A multidisciplinary panel of experts in oncology, nutrition, exercise, and medicine participated in a 2-day virtual roundtable in October 2020 to discuss gaps and opportunities in oncology nutrition, alone and in combination with exercise, relative to current evidence and international societies' recommendations. The panel recommended five principles to optimize clinical oncology practice: (1) position oncology nutrition at the center of multidisciplinary care; (2) partner with colleagues and administrators to integrate a nutrition care process into the multidisciplinary cancer care approach; (3) screen all patients for malnutrition risk at diagnosis and regularly throughout treatment; (4) combine exercise and nutrition interventions before (e.g., prehabilitation), during, and after treatment as oncology standard of care to optimize nutrition status and muscle mass; and (5) incorporate a patient-centered approach into multidisciplinary care.

Preliminary report of the effect of high-dose adjuvant intensity modulated radiation therapy on the sural nerve graft for cavernosal nerve sacrifice after radical prostatectomy.

PURPOSE: A sural nerve graft may replace a killed cavernosal nerve. The effect of intensity-modulated radiation therapy (IMRT) on function of the graft has not been reported. MATERIALS AND METHODS: Between 1998 and 2001, 8 patients (9 nerve grafts) were treated with postoperative IMRT (mean dose, 70 Gy). Two patients had neoadjuvant Lupron 30 mg 2 months prior to radiation. Potency was defined as ability to achieve spontaneous erection sufficient for vaginal penetration. Median follow-up was 31.6 months. RESULTS: Five patients (62.5%) who had erectile function after prostatectomy preserved spontaneous erectile function after radiation. Of these, 3 patients had both nerves resected (two receiving unilateral grafts and one receiving bilateral grafts) and 2 others had one graft and one nerve preserved. The impotent patients were impotent after surgery. CONCLUSION: High-dose postprostatectomy IMRT does not place sural nerve grafts at greater risk for failure. Larger numbers of patients are needed to confirm these encouraging, preliminary findings.

Long-term benefits of elective radiotherapy after prostatectomy for patients with positive surgical margins.

PURPOSE: The benefit of adjuvant radiotherapy after prostatectomy for patients with pathological risk factors but with an undetectable postoperative PSA remains controversial. In this retrospective study we define the benefits of elective postoperative radiotherapy in this setting. MATERIALS AND METHODS: A total of 44 patients received elective postoperative radiotherapy at a single institution in the PSA era (1989 to 1995) for positive surgical margins and undetectable postoperative PSA. Radiotherapy was delivered to a median dose of 60 Gy. Clinical target volume included the prostate bed. Pelvic nodes were not treated. The four-field box technique with customized blocking of bladder, rectum and small bowels was used and defined the planning target volume. The patients were then compared to a contemporaneous group of 189 patients with positive surgical margins who underwent radical prostatectomy without any adjuvant therapy. Failure was defined as biochemical (PSA) recurrence and was timed from first detectable PSA. RESULTS: The 5 and 10-year biochemical no evidence of disease was 90.9% and 90.9% for the elective postoperative radiotherapy group, and 66.4% and 54.5% for the observation group, respectively (p = 0.0012). Median time to biochemical failure was also longer in the elective postoperative radiotherapy group (88.6 months) compared to the observation group (43.5 months) (p <0.001). Risk factors for biochemical recurrence on multivariate analysis were Gleason score greater than 7 (p = 0.017), established extracapsular extension (p = 0.002) and lack of elective postoperative radiation (p = 0.001). CONCLUSIONS: This is one of the longest followup studies showing that elective postoperative radiation therapy is associated with improved bNED and prolonged time to recurrence. Combined radical prostatectomy and elective postoperative radiotherapy should be considered in the management of high risk prostate cancer, especially in the presence of positive surgical margins despite undetectable PSA.

Tolerance of endorectal balloon in 396 patients treated with intensity-modulated radiation therapy (IMRT) for prostate cancer.

PURPOSE: To report patient tolerance and acute anorectal toxicity of an endorectal balloon used for prostate immobilization during 35 daily fractions. MATERIALS AND METHODS: The records of 396 patients treated for prostate cancer from October 1997 to November 2001 were reviewed. Patients were treated with intensity modulated radiation therapy (IMRT). Endorectal balloon catheter was inserted daily, inflated with 100 mL of air for immobilizing the prostate gland. Patient and treatment factors were analyzed. Patients received a mean dose of 77 Gy/35 fractions/7 weeks with no rectal block. RESULTS: None of the 396 patients halted treatment because of associated ano-rectal toxicity. No patient stated that he would decline to be treated again with rectal balloon. Three of 396 (0.8%) patients required a reduction in the volume of the balloon to 50 mL. Seventeen of 396 (4.3%) patients required Lidocaine jelly with the insertion of balloon. Radiation Therapy Oncology Group (RTOG) grades 1 and 2 rectal toxicity occurred in 55/396 (13.9%) and 73/396 (18.4%), respectively. No RTOG grade 3 or 4 toxicities occurred. Topical anal medications were prescribed for 46 of 396 (11.6%) patients and antidiarrhea medication for 27 of 396 (6.8%) patients. Of patients with pretreatment anorectal disease, 50% developed rectal toxicities over the 7 weeks. Rectal toxicity occurred most frequently in the third, fourth, fifth, or sixth week; 19.5%, 20.8%, 18.2%, and 16.9%, respectively. The duration of the toxicity measured lasted 1 week, 35.2%; 2 weeks, 31.0%; 3 weeks, 15.5%; 4 weeks, 11.3%; 5 weeks, 4.2%; and 6 weeks, 2.8%. CONCLUSION: Most of the patients, 393/396 (99.2%), tolerated a 100 mL endorectal immobilization balloon for IMRT. The rate of acute anorectal toxicity was acceptable with no grade 3 or 4 toxicities. Duration of the toxicities typically was 1 to 2 weeks. Patients with pre-existing anorectal disease are at higher risk of developing acute anorectal toxicity with the use of an endorectal balloon.

IMRT for prostate cancer: defining target volume based on correlated pathologic volume of disease.

PURPOSE: The intensity-modulated radiation therapy (IMRT) treatment planning system generates tightly constricted isodose lines. It is very important to define the margins that are acceptable in the treatment of prostate cancer to maximize the dose escalation and normal tissue avoidance advantages offered by IMRT. It is necessary to take into account subclinical disease and the potential for extracapsular spread. Organ and patient motion as well as setup errors are variables that must be minimized and defined to avoid underdosing the tumor or overdosing the normal tissues. We have addressed these issues previously. The purpose of the study was twofold: to quantify the radial distance of extracapsular extension in the prostatectomy specimens, and to quantify differences between the pathologic prostate volume (PPV), CT-based gross tumor volume (GTV), and planning target volume (PTV). MATERIALS AND METHODS: Two related studies were undertaken. A total of 712 patients underwent prostatectomy between August 1983 and September 1995. Pathologic assessment of the radial distance of extracapsular extension was performed. Shrinkage associated with fixation was accounted for with a linear shrinkage factor. Ten patients had preoperative staging studies including a CT scan of the pelvis. The GTV was outlined and volume determined from these CT scans. The PTV, defined as GTV with a 5-mm margin in all dimensions, was then calculated. The Peacock inverse planning system (NOMOS Corp., Sewickley, PA) was used. The PPV, GTV, and PTV were compared for differences and evaluated for correlation. RESULTS: Extracapsular extension (ECE) (i.e., prostatic capsular invasion level 3 [both focal and established]) was found in 299 of 712 patients (42.0%). Measurable disease extending radially outside the prostatic capsule (i.e., ECE level 3 established) was noted in 185 of 712 (26.0%). The median radial extension was 2.0 mm (range 0.50-12.00 mm) outside the prostatic capsule. As a group, 20 of 712 (2.8%) had extracapsular extension of more than 5 mm. In the volumetric comparison and correlation study of the GTV and PTV to the PPV, the average GTV was 2 times larger than the PPV. The average PTV was 4.1 times larger than the PPV. CONCLUSIONS: This is the largest series in the literature quantitatively assessing prostatic capsular invasion (i.e., the radial extracapsular extension). It is the first report of a comparison of PPV to CT-planned GTV and PTV. Using patient and prostate immobilization, 5 mm of margin to the GTV in this study provided sufficient coverage of the tumor volume based on data gathered from 712 patients. In the absence of prostate immobilization, additional margins of differing amounts depending on the technique employed would have to be placed to account for target, patient, and setup uncertainties. The large mean difference between CT-based estimates of the tumor volume and target volume (GTV+PTV) and PPV added further evidence for adequacy of tumor coverage. Target immobilization, setup error, and coverage of subclinical disease must be addressed carefully before successful implementation of IMRT to maximize its ability to escalate dose and to spare normal tissue simultaneously and safely.

Predictors of extracapsular extension and its radial distance in prostate cancer: implications for prostate IMRT, brachytherapy, and surgery.

PURPOSE: Tightly constricted isodose lines are generated using brachytherapy or intensity-modulated radiation therapy (IMRT) treatment planning systems for prostate cancer. Definition of margins that encompass subclinical disease extension is important to maximize dose escalation while attemptingto adhere to normal tissue dose tolerances. In this study, we attempted to find predictors of extracapsular extension (ECE) and its radial distance. MATERIALS AND METHODS: Pathological assessment of ECE and its radial distance was performed on 712 radical prostatectomy specimens. Preoperative data (initial prostate-specific antigen, clinical stage, ultrasound volume, and biopsy Gleason score) were evaluated for their ability to predict the presence of ECE and its radial distance. RESULTS: Measurable disease was noted outside the prostatic capsule in 185 of 712 (26.0%) specimens. All preoperative parameters except ultrasound volume were able to predict the presence of ECE. However, none of them was predictive of the radial ECE distance. In this group, the median and the range of the maximum depth of invasion (radial extension from the capsule) were 2.00 and 0.5-12.00 mm, respectively. The mean radial distance from the capsule was 2.93 mm, SD +/- 2.286 mm. All subgroups had some patients with radial extension ranging from 0-2 mm, 2-5 mm, to > 5 mm. Only patients with a prostate-specific antigen of 0-4 ng/mL had no extension > 5 mm. CONCLUSIONS: This is the largest series in the literature thus far that quantitatively assesses radial extracapsular extension. Coverage of subclinical disease must be addressed carefully before successful implementation of intensity-modulated radiation therapy, brachytherapy, or prostatectomy in order to avoid geographical miss.

Post-nerve-sparing prostatectomy, dose-escalated intensity-modulated radiotherapy: effect on erectile function.

PURPOSE: The advent of widespread prostate-specific antigen screening has resulted in more younger, potent men being diagnosed with early-stage, organ-confined prostate cancer amenable to definitive surgery. Nerve-sparing prostatectomy is a relatively new surgical advance in the treatment of prostate cancer. Very few data exist on the effect of postoperative radiotherapy (RT) on erectile function after nerve-sparing prostatectomy. They are based on conventional techniques using moderate doses of radiation, 45-54 Gy. Intensity-modulated RT (IMRT) is becoming more widespread because it allows dose escalation with increased sparing of the surrounding normal tissue. We investigated the effect of postprostatectomy, high-dose IMRT on patients' erectile function. METHODS AND MATERIALS: A review of patient records found 51 patients treated between April 1998 and December 2000 with IMRT after unilateral or bilateral nerve-sparing prostatectomy. The pathologic disease stage in these patients was T2 in 47.4% and T3 in 52.6%. Postoperatively, 4 patients received hormonal ablation consisting of one injection of Lupron Depot (30 mg) 2 months before RT. The median age was 65 years (range 46-77) at the time of RT. The prescribed dose was 64 Gy (range 60-66). The mean dose was 69.6 Gy (range 64.0-72.3). Erectile function was assessed before and after RT by questionnaires. Sexual potency was defined as erectile rigidity adequate for vaginal penetration. RESULTS: Of the 51 patients, 18 (35.3%) maintained their potency and 33 (64.7%) became impotent after nerve-sparing prostatectomy. Patients who underwent bilateral nerve-sparing prostatectomy had higher rates of postoperative potency than did those who underwent unilateral nerve-sparing surgery (72.2% vs. 27.8%; p = 0.025). The follow-up for the entire group was 19.5 months. All 18 patients (100%) who were potent postoperatively remained potent after RT. The median follow-up for the 18 potent patients was 27.2 months, significantly longer than that of the impotent group, 13.0 months (p <0.001). CONCLUSION: This is the first report on the effects of dose-escalated IMRT on men who have undergone nerve-sparing prostatectomy. Despite the high dose (mean dose 69.6 Gy) to the prostate bed and nerves, postoperative IMRT had no negative effect on erectile function for the patients who remained potent after nerve-sparing prostatectomy. Longer term follow-up and a larger cohort of patients are warranted to confirm these findings.