Eric M. Horwitz

Adaptive modification of treatment planning to minimize the deleterious effects of treatment setup errors

PURPOSEnUsing daily setup variation measured from an electronic portal imaging device (EPID), radiation treatment of the individual patient can be adaptively reoptimized during the course of therapy. In this study, daily portal images were retrospectively examined to: (a) determine the number of initial days of portal imaging required to give adequate prediction of the systematic and random setup errors; and (b) explore the potential of using the prediction as feedback to reoptimize the individual treatment part-way through the treatment course.nnnMETHODS AND MATERIALSnDaily portal images of 64 cancer patients, whose treatment position was not adjusted during the course of treatment, were obtained from two independent clinics with similar setup procedures. Systematic and random setup errors for each patient were predicted using different numbers of initial portal measurements. The statistical confidence of the predictions was tested to determine the number of daily portal measurements needed to give reasonable predictions. Two treatment processes were simulated to examine the potential opportunity for setup margin reduction and dose escalation. The first process mimicked a conventional treatment. A constant margin was assigned to each treatment field to compensate for the average setup error of the patient population. A treatment dose was then prescribed with reference to a fixed normal tissue tolerance, and then fixed in the entire course of treatment. In the second process, the same treatment fields and prescribed dose were used only for the initial plan and treatment. After several initial days of treatments, the treatment field shape and position were assumed to be adaptively modified using a computer-controlled multileaf collimator (MLC) in light of the predicted systematic and random setup errors. The prescribed dose was then escalated until the same normal tissue tolerance, as determined in the first treatment process, was reached.nnnRESULTSnThe systematic setup error and the random setup error were predicted to be within +/-1 mm for the former and +/-0.5 mm for the latter at a > or = 95% confidence level using < or = 9 initial daily portal measurements. In the study, a large number of patients could be treated using a smaller field margin if the adaptive modification process were used. Simulation of the adaptive modification process for prostate treatment demonstrates that additional treatment dose could be safely applied to 64% of patients.nnnCONCLUSIONnThe adaptive modification process represents a different approach for use of on-line portal images. The portal imaging information from the initial treatments is used as feedback for reoptimization of the treatment plan, rather than adjustment of the treatment setup. Results from the retrospective study show that the treatment of individual patient can be improved with the adaptive modification process.

Irradiation of the tumor bed alone after lumpectomy in selected Patients with early-stage breast cancer treated with breast conserving therapy

We present the interim findings of our in‐house protocol treating the tumor bed alone after lumpectomy with low‐dose‐rate (LDR) interstitial brachytherapy in selected patients with early‐stage breast cancer treated with breast conserving therapy (BCT).

THE CORRELATION BETWEEN THE ASTRO CONSENSUS PANEL DEFINITION OF BIOCHEMICAL FAILURE AND CLINICAL OUTCOME FOR PATIENTS WITH PROSTATE CANCER TREATED WITH EXTERNAL BEAM IRRADIATION

PURPOSEnWe reviewed our institutions experience treating patients with external beam irradiation (RT) to determine if the ASTRO Consensus Panel definition of biochemical failure (BF) following radiation therapy correlates with clinical distant metastases free survival (DMFS), disease-free survival (DFS), cause-specific survival (CSS), and local control (LC).nnnMETHODS AND MATERIALSnBetween 1/1/87 and 12/31/92, 568 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital (median total dose 66.6 Gy; range: 60-70.4 Gy). Biochemical failure was defined as three consecutive increases in post-treatment prostate specific antigen (PSA) after achieving a nadir. Biochemical failure was recorded as the time midway between the nadir and the first rising PSA. Five-year actuarial rates of clinical DMFS, DFS, CSS, and LC were calculated for patients who were biochemically controlled (BC) versus those who failed biochemically. Median follow-up was 56 months (range: 24-118 months).nnnRESULTSnFive-year actuarial rates of DMFS, DFS, CSS, and LC were significantly greater in patients who were biochemically controlled versus those who were not (p < 0.001). In patients who were BC, the 5-year actuarial rates of DMFS, DFS, CSS, and LC were 99%, 99%, 98%, and 99% respectively. For patients who failed biochemically, the 5-year actuarial rates of DMFS, DFS, CSS, and LC were 74%, 64%, 89%, and 86% respectively. When stratifying by pretreatment PSA, Gleason score, and T stage these differences remained significant for DMFS, DFS, and CSS. The Cox proportional hazards model demonstrated that BC was the single most important predictor of clinical outcome for DMFS, DFS, CSS, and LC. Pretreatment PSA and Gleason score were also independent predictors of outcome for DMFS and DFS.nnnCONCLUSIONSnThe ASTRO Consensus Panel definition of BF following radiation therapy correlates well with clinical DMFS, DFS, and CSS. These findings suggest that the Consensus Panel definition may be a surrogate for clinical progression and survival and should be considered a valid endpoint for separating successful versus unsuccessful treatment. Additional studies with longer follow-up will be needed to corroborate these findings.

The role of regional nodal irradiation in the management of patients with early-stage breast cancer treated with breast-conserving therapy

PURPOSEnTo determine the incidence of regional nodal failure (RNF) and indications for regional nodal irradiation (RNI) in patients with Stage I and II breast cancer treated with breast-conserving therapy (BCT).nnnMETHODS AND MATERIALSnFour hundred fifty-six patients with Stage I/II breast cancer were treated with BCT at William Beaumont Hospital. All patients underwent excisional biopsy and 288 (63%) were reexcised. A Level I/II ipsilateral axillary lymph node dissection was performed on 431 patients (95%). Pathologically involved nodes were found in 106 (23%) cases (69 with one to three nodes and 37 with > or = four nodes involved). All patients received whole breast irradiation (median dose 50 Gy) and 415 (91%) were boosted to the tumor bed (median total dose 60.4 Gy). Three hundred and sixty (79%) patients received breast alone irradiation and 96 (21%) also received RNI. The median axilla/supraclavicular fossa dose was 50 Gy.nnnRESULTSnWith a median follow-up of 83 months, 15 patients developed a RNF for a 5- and 8-year actuarial rate of 3 and 4%, respectively. The 5- and 8-year actuarial rates of axillary failure (AF) were 0.7 and 1.0%, respectively. The incidence of RNF or AF was not affected by the use of RNI in N0 or N1 patients with one to three positive nodes. Only in patients with four or more positive nodes was there a trend towards improved regional control with RNI (p = 0.09). However, patient numbers were extremely small, and this improvement was limited to a reduction in the rate of failure in the supraclavicular fossa (SCF) (20 vs. 0%, p = 0.04). Multiple clinical, pathologic, and treatment related factors were analyzed for an association with AF. On univariate analysis, AF was associated with the number of lymph nodes excised (p < 0.0001) estrogen receptor status (p = 0.0016), and pathologic node status (p = 0.0021).nnnCONCLUSIONSnRegional nodal failure as the first site of failure is uncommon in patients with early-stage breast cancer treated with BCT with < or = three positive lymph nodes and appears unaffected by RNI. For patients with four or more positive lymph nodes, a trend towards improved RNF was noted with RNI, primarily in the SCF. However, patient numbers were extremely small in all subsets analyzed. Additional studies are needed to further define the need for RNI in these patients and help determine other factors associated with RNF.

Assessing the variability of outcome for patients treated with localized prostate irradiation using different definitions of biochemical control

PURPOSEnBiochemical control using serial posttreatment serum prostate specific antigen (PSA) levels is being increasingly used to assess treatment efficacy for localized prostate cancer. However, no standardized definition of biochemical control has been established. We reviewed our experience treating patients with localized prostate cancer and applied three different commonly used definitions of biochemical control to determine if differences in therapeutic outcome would be observed.nnnMETHODS AND MATERIALSnBetween January 1987 and December 1991, 480 patients with clinically localized prostate cancer received external beam irradiation (RT) using localized prostate fields at William Beaumont Hospital. The median dose to the prostate was 66.6 Gy (range 58-70.4) using a four-field or arc technique. Pretreatment and posttreatment serum PSA levels were recorded. Over 86% (414 of 480) of patients had a pretreatment PSA level available. Three different definitions of biochemical control were used: (a) PSA nadir < 1 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (b) PSA nadir < 1.5 ng/ml within 1 year of treatment completion. After achieving nadir, if two consecutive increases of PSA were noted, the patient was scored a failure at the time of the first increase; (c) Posttreatment PSA nadir < 4 ng/ml without a time limit. Once the nadir was achieved, if it did not rise above normal the patient was considered to be biochemically controlled. Clinical local control was defined as no palpable prostate nodularity beyond 18 months, no new prostate nodularity, or a negative prostate biopsy.nnnRESULTSnMedian follow-up was 48 months (range 3-112). Pretreatment PSA values were correlated with treatment outcome using the three definitions of biochemical control as well as clinical local control. Pretreatment PSA values were stratified into five groups (Group 1: PSA < 4; Group 2: PSA 4-10; Group 3: PSA 10-15; Group 4: PSA 15-20; and Group 5: PSA > 20), and 5-year actuarial rates of biochemical control were calculated using the three biochemical control and one clinical local control definitions. For Group 1, 5-year actuarial rates of biochemical control were 84%, 90%, 91%, and 96% for Definitions 1-3 and clinical local control, respectively. For Group 2, 5-year actuarial control rates were 45%, 54%, 74%, and 92% for the four definitions, respectively. For Group 3, 5-year actuarial control rates were 26%, 31%, 63%, and 100% for the four definitions, respectively. For Group 4, 5-year actuarial control rates were 24%, 24%, 50%, and 100% for the four definitions, respectively. Finally, for Group 5, 5-year actuarial control rates were 5%, 14%, 15%, and 89% for the four definitions, respectively. Depending on the definition used, statistically significant differences overall in outcome rates were observed. Differences between all four definitions for all pairwise comparisons ranged from 5 to 53% (p < 0.001).nnnCONCLUSIONnWhen different definitions of biochemical control are used in assessing treatment outcome, significantly different rates of success are noted. Until a standardized definition of biochemical control is adopted, differences in treatment outcome cannot be meaningfully compared.

Implementation of 3D-virtual brachytherapy in the management of breast cancer: a description of a new method of interstitial brachytherapy.

PURPOSEnWe present the initial description of a new technique of interstitial breast brachytherapy in which a computer-generated image of an implant template is applied virtually to serial-computed tomography (CT) scan images of a patients breast. Optimal placement of the virtual template around the CT images of the proposed target volume provides the physician with a preplan for improved positioning of implant needles around the actual target volume intraoperatively.nnnMETHODS AND MATERIALSnSince March of 1993, 110 patients with early-stage breast cancer were entered onto a protocol of low or high dose rate brachytherapy as the sole radiation modality for part of their breast-conserving therapy. To improve the accuracy and reproducibility of target volume coverage in patients with a closed lumpectomy cavity, 11 of these implants were performed using the virtual brachytherapy technique. The virtual implant procedure was performed by first placing radiopaque skin markers on the breast surface for reference on the CT image and ultimately as intraoperative landmarks for the placement of implant needles. A CT scan of the breast was then performed and the target volume outlined on each CT scan slice by the physician. A virtual image of the brachytherapy template was then positioned around the CT image of the target volume to achieve an idealized implant with optimal coverage. The projected entrance and exit points of all needles on the skin of the breast (from the idealized virtual implant) were then identified (by perspective rendering of multiple 3D views) and hard-copy images taken to the operating room. The implant was then constructed by referencing the virtual implant images (needle entrance and exit points) to the radiopaque skin markers on the breast. After the implant was completed, a CT scan of the breast with the template catheters or needles in position was taken for comparison of the actual target volume coverage with the virtual implant generated preoperatively.nnnRESULTSnIntraoperative ultrasound was used to check the real-time position of the afterloading needles in reference to the chest wall and posterior border of the target volume. No adjustment of needles was required in any of the 11 patients. Assessment of target volume coverage between the virtual implant and the actual CT image of the implant showed excellent agreement. In each case, all target volume boundaries specified by the physician were adequately covered. The total number of implant planes, intertemplate separation, and template orientation were identical between the virtual and real implant.nnnCONCLUSIONnWe conclude that 3D virtual brachytherapy may offer an improved technique for accurately performing interstitial implants of the breast with a closed lumpectomy cavity in selected patients. Although preliminary results show excellent coverage of the desired target volume, additional patients will be required to establish the reproducibility of this technique and its practical limitations.

Excellent functional outcome in patients with squamous cell carcinoma of the base of tongue treated with external irradiation and interstitial iodine 125 boost

Local control, functional outcome, and complications in patients with carcinoma of the base of tongue (BOT) were analyzed to assess the impact of interstitial implant boost with I‐125 seeds.

Long term results with breast‐conserving therapy for patients with early stage breast carcinoma in a community hospital setting

Prospective randomized trials and retrospective reviews from academic centers have documented the success of breast‐conserving therapy (BCT) for patients with early stage breast carcinoma. The authors retrospectively reviewed the outcome of BCT for early stage breast carcinoma to determine the success of BCT at the study institution, a 1000‐bed community hospital.

Treatment Options for Localized Prostate Cancer Based on Pretreatment Serum Prostate Specific Antigen Levels

PURPOSEnWe reviewed all available literature on early stage prostate cancer treatment in which pretreatment serum prostate specific antigen (PSA) levels were used to stratify patients. We determined if any conclusions could be reached regarding the optimal therapy of this disease.nnnMATERIALS AND METHODSnA MEDLINE search was conducted to obtain all articles in English on prostate cancer treatment from 1986 to 1996 in which PSA levels were used to stratify patients and evaluate outcome. Studies were considered eligible only if they met all criteria of pretreatment PSA values recorded and grouped for subsequent evaluation, posttreatment PSA values monitored continuously, definitions of biochemical control stated and median followup given.nnnRESULTSnOf the 16 surgical studies identified only 3 met the inclusion criteria. Of the 30 radiation therapy articles identified 15 met the inclusion criteria, including 2 on conformal external beam radiotherapy, 8 on conventional external beam radiotherapy and 5 on interstitial brachytherapy. No studies using neutrons or combined hormonal therapy with surgery or radiotherapy were identified in which patients were stratified by pretreatment PSA. Results for all therapies were extremely variable with the 3 to 5-year rates of biochemical control ranging from 48 to 100% for patients with a pretreatment PSA of less than 4 ng./ml., 44 to 90% for PSA more than 4 to 10 ng./ml. and 27 to 89% for PSA more than 10 to 20 ng./ml. Even using the same treatment modality, a wide range of results were obtained. No treatment option consistently produced superior results.nnnCONCLUSIONSnWhen data were reviewed from studies using pretreatment serum PSA to stratify patients, no consistently superior treatment option in the radiotherapy or surgical literature emerged. These data suggest that standard definitions of disease stage and biochemical cure must be adopted to evaluate treatment efficacy and advise patients on the most appropriate treatment option for the disease.

Ductal carcinoma in situ detected in the mammographic era: An analysis of clinical, pathologic, and treatment-related factors affecting outcome with breast-conserving therapy

PURPOSEnWe reviewed our institutions experience treating predominantly mammographically detected ductal carcinoma in situ (DCIS) with breast-conserving therapy (BCT) to determine if any clinical, pathologic, or treatment-related factors affected outcome.nnnMETHODS AND MATERIALSnFrom January 2, 1980 to January 6, 1992, 107 breasts in 105 patients were treated with BCT at William Beaumont Hospital, Royal Oak, MI. All patients underwent at least an excisional biopsy and 70 patients (65%) were reexcised. All patients received whole-breast irradiation to a median dose of 50.4 Gy (range 43.1 to 56.0 Gy). Ninety-nine patients (93%) received a supplemental boost to the tumor bed for a median total dose of 60.4 Gy (range 59.1 to 71.8 Gy) using either photons (2 patients), electrons (69 patients), or an interstitial implant (28 patients).nnnRESULTSnWith a median follow-up of 78 months, 10 patients have failed in the treated breast for a 5- and 10-year actuarial local control rate of 91.2 and 89.8%, respectively. Thirteen percent of the population have been followed for 10 years or more. Three recurrences were pure DCIS, and seven were invasive. All patients were salvaged with mastectomy. Nine patients remain without evidence of disease a median of 30.6 months after surgery. One patient failed distantly 36 months after local recurrence for an ultimate cause specific survival of 99%. Potential clinical (age, mammographic findings, method of detection, etc.), pathologic (nuclear grade, margins, etc.), and treatment-related factors (dose, boost technique, reexcision status, etc.) affecting outcome were analyzed. No variable was found to be associated with an ipsilateral breast tumor recurrence. However, when only recurrences that occurred within or immediately adjacent to the lumpectomy cavity were analyzed, both margin status and the extent of cancerization of lobules (COL) near the surgical margin were associated with the development of a local recurrence.nnnCONCLUSIONSnPatients treated with BCT for predominantly mammographically detected DCIS achieve excellent rates of local control and overall survival. Both margin status and the extent of COL near the surgical margin appear to be associated with recurrences within or immediately adjacent to the lumpectomy cavity. These data suggest that careful attention to the completeness of surgical resection of DCIS is an important determinant of outcome.